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Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02648724
Recruitment Status : Completed
First Posted : January 7, 2016
Results First Posted : June 22, 2022
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Oncology
MET Gene Amplification
NSCLC
MET Gene Mutation
Non Small Cell Lung Cancer
Intervention Drug: Sym015
Enrollment 57
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1: Dose-Escalation; Period 1: 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Hide Arm/Group Description

Patients received 6 mg/kg Symp015.

Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 12 mg/kg Symp015.

Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 18 mg/kg Symp015.

Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 24 mg/kg Symp015-.

Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

Basket Cohort:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

NSCLC MET-Amplified Cohort:

Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

NSCLC METex14del Cohort:

Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Period Title: Overall Study
Started 3 3 3 3 25 8 12
Completed 0 0 0 0 0 0 0
Not Completed 3 3 3 3 25 8 12
Reason Not Completed
Withdrawal by Subject             0             1             1             0             1             0             0
Progressive disease             2             2             2             3             22             7             8
Other reason (unknown)             1             0             0             0             0             0             0
Protocol Violation             0             0             0             0             1             0             0
Death             0             0             0             0             0             0             3
Physician Decision             0             0             0             0             1             0             1
Transferred to named patient program             0             0             0             0             0             1             0
Arm/Group Title Part 1: Dose-Escalation, 6 mg/kg Part 1: Dose-Escalation, 12 mg/kg Part 1: Dose-Escalation 18 mg/kg Part 1: Dose-Escalation 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METex14del Cohort Total
Hide Arm/Group Description

Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients with advanced NSCLC with MET-amplification received Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients with advanced NSCLC with METex14del received Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 3 25 8 12 57
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
55.7  (14.57) 62.0  (11.79) 55.3  (11.24) 67.3  (7.23) 56.6  (11.87) 65.6  (8.91) 68.5  (9.82) 61.1  (11.73)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
18-65 years
2
  66.7%
1
  33.3%
2
  66.7%
1
  33.3%
20
  80.0%
2
  25.0%
6
  50.0%
34
  59.6%
65 to <75 years
1
  33.3%
2
  66.7%
1
  33.3%
2
  66.7%
4
  16.0%
5
  62.5%
0
   0.0%
15
  26.3%
75 to <85 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
1
  12.5%
6
  50.0%
8
  14.0%
85 years or older
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Female
1
  33.3%
2
  66.7%
2
  66.7%
2
  66.7%
7
  28.0%
5
  62.5%
6
  50.0%
25
  43.9%
Male
2
  66.7%
1
  33.3%
1
  33.3%
1
  33.3%
18
  72.0%
3
  37.5%
6
  50.0%
32
  56.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
2
  66.7%
1
   4.0%
0
   0.0%
1
   8.3%
4
   7.0%
Not Hispanic or Latino
3
 100.0%
3
 100.0%
3
 100.0%
1
  33.3%
24
  96.0%
8
 100.0%
11
  91.7%
53
  93.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
14
  56.0%
2
  25.0%
1
   8.3%
17
  29.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
2
   3.5%
White
2
  66.7%
3
 100.0%
3
 100.0%
2
  66.7%
8
  32.0%
6
  75.0%
11
  91.7%
35
  61.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
   4.0%
0
   0.0%
0
   0.0%
2
   3.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
South Korea 0 0 0 0 12 2 0 14
United States 3 3 3 3 6 3 8 29
Taiwan 0 0 0 0 1 0 0 1
Denmark 0 0 0 0 0 1 1 2
Spain 0 0 0 0 6 2 3 11
Body weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
82.2  (17.86) 62.5  (12.03) 89.0  (18.29) 69.7  (8.05) 67.1  (10.73) 60.3  (11.58) 72.1  (15.54) 69.1  (13.86)
Body mass index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg per square meter
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
28.10  (1.132) 23.65  (3.978) 29.84  (7.452) 25.89  (5.363) 23.58  (3.776) 22.15  (4.590) 25.19  (4.081) 24.44  (4.405)
[1]
Measure Analysis Population Description: BMI was not evaluable for all participants
ECOG-PS   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
0
1
  33.3%
2
  66.7%
1
  33.3%
0
   0.0%
4
  16.0%
2
  25.0%
1
   8.3%
11
  19.3%
1
2
  66.7%
1
  33.3%
2
  66.7%
3
 100.0%
21
  84.0%
6
  75.0%
9
  75.0%
44
  77.2%
2
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  16.7%
2
   3.5%
[1]
Measure Description:

ECOG-PS=Eastern Cooperative Oncology Group performance status. It describes patient functioning level on a 5 graded scale.

Grade 0: Fully active, able to carry on all pre-disease performance without restriction Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours Grade 3-5: Ranges from capable of only limited selfcare to dead.

Site of primary tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Breast
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
2
   3.5%
Colon
2
  66.7%
1
  33.3%
0
   0.0%
0
   0.0%
2
   8.0%
0
   0.0%
0
   0.0%
5
   8.8%
Genitourinary
0
   0.0%
1
  33.3%
1
  33.3%
0
   0.0%
3
  12.0%
0
   0.0%
0
   0.0%
5
   8.8%
Hepatic (including gallbladder)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Liver
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  12.0%
0
   0.0%
0
   0.0%
3
   5.3%
Neck
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Other locally advanced sites
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
3
  12.0%
1
  12.5%
0
   0.0%
5
   8.8%
Other metastatic sites
0
   0.0%
0
   0.0%
1
  33.3%
1
  33.3%
1
   4.0%
0
   0.0%
0
   0.0%
3
   5.3%
Pancreas
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Respiratory
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7
  87.5%
12
 100.0%
19
  33.3%
Skin/soft tissue
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Gastrointestinal
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
11
  44.0%
0
   0.0%
0
   0.0%
11
  19.3%
Histopathologic diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Adenocarcinoma
3
 100.0%
1
  33.3%
1
  33.3%
2
  66.7%
22
  88.0%
7
  87.5%
11
  91.7%
47
  82.5%
Missing
0
   0.0%
2
  66.7%
2
  66.7%
1
  33.3%
3
  12.0%
1
  12.5%
1
   8.3%
10
  17.5%
Anatomic based cancer type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Adenocarcinoma of Parotid Gland
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Adenocarcinoma of Thymus
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
BRCA (breast cancer gene)
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
2
   3.5%
CRC (colorectal cancer)
2
  66.7%
1
  33.3%
0
   0.0%
0
   0.0%
3
  12.0%
0
   0.0%
0
   0.0%
6
  10.5%
Cholangiocarcinoma
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
GC (gastric cancer)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
13
  52.0%
0
   0.0%
0
   0.0%
13
  22.8%
GU (genitourinary cancer)
0
   0.0%
1
  33.3%
1
  33.3%
0
   0.0%
3
  12.0%
0
   0.0%
0
   0.0%
5
   8.8%
HCC (hepatocellular carcinoma)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   8.0%
0
   0.0%
0
   0.0%
2
   3.5%
HCC-MIXED
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
HCC-Neuroendocrine
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Lung-Neuroendocrine
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
NSCLC (non-small-cell lung carcinoma)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7
  87.5%
11
  91.7%
18
  31.6%
NSCLC- Sq type
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
1
   8.3%
2
   3.5%
Nasopharyngeal carcinoma
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Pancreatic cancer
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
SCC (squamous cell carcinoma) of skin/soft tissue
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Time since initial diagnosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
4.7  (2.52) 2.3  (1.53) 10.3  (9.29) 2.0  (2.0) 2.1  (2.20) 0  (0) 0  (0) 3.5  (4.57)
[1]
Measure Analysis Population Description: Data were not available for all patients in Part 2
Previous debulking surgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
No
3
 100.0%
1
  33.3%
2
  66.7%
3
 100.0%
16
  64.0%
7
  87.5%
12
 100.0%
44
  77.2%
Yes
0
   0.0%
2
  66.7%
1
  33.3%
0
   0.0%
9
  36.0%
1
  12.5%
0
   0.0%
13
  22.8%
Sites with metastasis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
Abdomen, pelvis
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Abdominal cavity, diaphragm, subcutis, para- renal mass, Sub-Hepatic Mass
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Adrenal gland
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
4
  16.0%
1
  12.5%
4
  33.3%
10
  17.5%
Bone
1
  33.3%
0
   0.0%
2
  66.7%
2
  66.7%
6
  24.0%
2
  25.0%
7
  58.3%
20
  35.1%
Both ovaries, peritoneum, colon
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Brain
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
   4.0%
2
  25.0%
1
   8.3%
5
   8.8%
Duodenum
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Effusion
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Kidney
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  16.7%
2
   3.5%
Liver
2
  66.7%
2
  66.7%
0
   0.0%
2
  66.7%
8
  32.0%
1
  12.5%
2
  16.7%
17
  29.8%
Lungs
1
  33.3%
2
  66.7%
2
  66.7%
2
  66.7%
8
  32.0%
7
  87.5%
9
  75.0%
31
  54.4%
Lymph nodes
2
  66.7%
3
 100.0%
0
   0.0%
3
 100.0%
20
  80.0%
6
  75.0%
7
  58.3%
41
  71.9%
Lymph nodes and Lymphangitis Carcinomatoses
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
1
   1.8%
Muscle
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
1
   1.8%
Pelvis, abdominal wall, spleen
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Peritoneal
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   8.0%
0
   0.0%
0
   0.0%
2
   3.5%
Peritoneum, peribiliary
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Pleura
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  16.7%
2
   3.5%
Pleural based metastases
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Primary gastric cancer
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Rectum
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
1
   1.8%
Skin
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
2
   3.5%
Soft tissue
0
   0.0%
1
  33.3%
1
  33.3%
1
  33.3%
2
   8.0%
0
   0.0%
3
  25.0%
8
  14.0%
Spleen, pelvis, abdomen, left ovary
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Subpleura
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
1
   1.8%
Thyroid gland
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
Number of sites with metastasis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 25 participants 8 participants 12 participants 57 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
1
  33.3%
0
   0.0%
1
  33.3%
0
   0.0%
7
  28.0%
2
  25.0%
1
   8.3%
12
  21.1%
2
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
8
  32.0%
1
  12.5%
3
  25.0%
13
  22.8%
3
0
   0.0%
2
  66.7%
1
  33.3%
1
  33.3%
6
  24.0%
3
  37.5%
4
  33.3%
17
  29.8%
More than 3
1
  33.3%
1
  33.3%
1
  33.3%
2
  66.7%
4
  16.0%
2
  25.0%
4
  33.3%
15
  26.3%
1.Primary Outcome
Title Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
Hide Description The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.
Time Frame Cycle 1, the initial 28-day period of Q2W dosing
Hide Outcome Measure Data
Hide Analysis Population Description
For evaluation of DLTs, the DLT analysis set was used. This comprised all patients enrolled in Part 1 who had received at least one dose of Sym015, except patients who did not complete Cycle 1 (i.e., the initial 28-day period of Q2W dosing) for reasons other than drug toxicity.
Arm/Group Title Part 1: Dose-Escalation; Period 1, 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg
Hide Arm/Group Description:

Patients received 6 mg/kg Sym015.

Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET

Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Overall Number of Participants Analyzed 3 3 3 3
Measure Type: Number
Unit of Measure: Number of DLTs
0 0 0 0
2.Primary Outcome
Title Part 2: Documented, Confirmed Objective Response (OR)
Hide Description

The primary objective of Part 2 was to evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the different cohorts. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).

Q2W = every second week. RP2D = recommended phase 2 dose.

Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Arm/Group Title Part 2: Basket Cohort Part 2: Patients in NSCLC MET-Amplified Cohort Part 2: Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.
Overall Number of Participants Analyzed 25 8 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
  25.0%
3
  25.0%
3.Secondary Outcome
Title Part 1: Determine a Q2W RP2D of Sym015.
Hide Description Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
Time Frame 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
It was not possible to determine this endpoint as no DLTs were observed. The RP2D combination was not established and was instead chosen based on other safety findings as well as pharmacokinetic data, as described in the protocol.
Arm/Group Title Part 1: Dose-Escalation (4 Arms Combined)
Hide Arm/Group Description:

Sym015 was tested in four dose titration cohorts (6, 12, 18 and 24 mg/kg) with 3 patients per dose level. A substitute or an additional dose level could potentially be evaluated.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: mg/kg
NA [1] 
[1]
RP2D was not established as no DLTs were observed.
4.Secondary Outcome
Title Immunogenicity of Sym015: Part 1.
Hide Description Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Time Frame Cycle 1: Day (D) 1, Cycle 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 3 3 3
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 - day 1 Not done
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Negative
3
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
Patient withdrawn
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 3 - day 1 Not done
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Negative
1
  33.3%
0
   0.0%
2
  66.7%
0
   0.0%
Patient withdrawn
2
  66.7%
3
 100.0%
1
  33.3%
3
 100.0%
End of treatment Not done
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
Negative
3
 100.0%
2
  66.7%
1
  33.3%
2
  66.7%
Patient withdrawn
0
   0.0%
1
  33.3%
2
  66.7%
0
   0.0%
1-month follow-up Not done
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
Negative
2
  66.7%
1
  33.3%
0
   0.0%
2
  66.7%
Patient withdrawn
1
  33.3%
1
  33.3%
3
 100.0%
1
  33.3%
5.Secondary Outcome
Title Immunogenicity of Sym015: Part 2.
Hide Description Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Time Frame Cycle 1: Day (D) 1, Cycle 2, 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Arm/Group Title Part 2: Basket Cohort Part 2: Patients in NSCLC MET-Amplified Cohort Part 2: Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.
Overall Number of Participants Analyzed 25 8 12
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 - day 1 Not done
0
   0.0%
0
   0.0%
0
   0.0%
Negative
25
 100.0%
8
 100.0%
12
 100.0%
Positive
0
   0.0%
0
   0.0%
0
   0.0%
Patient withdrawn
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 2 - day 1 Not done
1
   4.0%
0
   0.0%
0
   0.0%
Negative
21
  84.0%
8
 100.0%
11
  91.7%
Positive
0
   0.0%
0
   0.0%
0
   0.0%
Patient withdrawn
3
  12.0%
0
   0.0%
1
   8.3%
Cycle 3 - day 1 Not done
1
   4.0%
1
  12.5%
0
   0.0%
Negative
8
  32.0%
7
  87.5%
8
  66.7%
Positive
0
   0.0%
0
   0.0%
0
   0.0%
Patient withdrawn
16
  64.0%
0
   0.0%
4
  33.3%
Cycle 5 - day 1 Not done
0
   0.0%
0
   0.0%
1
   8.3%
Negative
6
  24.0%
6
  75.0%
5
  41.7%
Positive
0
   0.0%
0
   0.0%
0
   0.0%
Patient withdrawn
19
  76.0%
2
  25.0%
6
  50.0%
Cycle 7 - day 1 Not done
0
   0.0%
1
  12.5%
0
   0.0%
Negative
2
   8.0%
2
  25.0%
5
  41.7%
Positive
0
   0.0%
0
   0.0%
0
   0.0%
Patient withdrawn
23
  92.0%
5
  62.5%
7
  58.3%
End of treatment Not done
5
  20.0%
0
   0.0%
0
   0.0%
Negative
15
  60.0%
7
  87.5%
9
  75.0%
Positive
1
   4.0%
0
   0.0%
0
   0.0%
Patient withdrawn
4
  16.0%
1
  12.5%
3
  25.0%
1-month follow up Not done
0
   0.0%
1
  12.5%
1
   8.3%
Negative
10
  40.0%
3
  37.5%
5
  41.7%
Positive
1
   4.0%
0
   0.0%
0
   0.0%
Patient withdrawn
14
  56.0%
4
  50.0%
6
  50.0%
6.Secondary Outcome
Title Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose
Hide Description Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 3 3 3
Median (Full Range)
Unit of Measure: h*μg/mL
17900
(17100 to 24500)
35700
(31600 to 42900)
82500
(75200 to 86200)
76800
(55200 to 86400)
7.Secondary Outcome
Title Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)
Hide Description Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose Expansion): Basket Cohort Part 2 (Dose Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 25 8 12
Median (Full Range)
Unit of Measure: h*ug/mL
34000
(17300 to 51800)
37200
(22000 to 55000)
38700
(11300 to 54000)
8.Secondary Outcome
Title Part 1: Cmax
Hide Description Maximum serum concentration was derived from observed data.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 3 3 3
Median (Full Range)
Unit of Measure: ug/mL
146
(141 to 151)
286
(275 to 323)
563
(419 to 711)
561
(379 to 726)
9.Secondary Outcome
Title Part 2: Cmax
Hide Description Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose-Expansion): Basket Cohort Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 25 8 12
Median (Full Range)
Unit of Measure: ug/mL
420
(310 to 700)
520
(320 to 610)
510
(330 to 1180)
10.Secondary Outcome
Title Part 1: Time to Reach Maximum Concentration (Tmax)
Hide Description Time to reach maximum concentration (Tmax) was derived from observed data.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 3 3 3
Median (Full Range)
Unit of Measure: hours
2.1
(2 to 5)
1.1
(1 to 2)
3.5
(3 to 4)
3.0
(3 to 9)
11.Secondary Outcome
Title Part 2: Time to Reach Maximum Concentration (Tmax)
Hide Description Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose-Expansion): Basket Cohort Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 25 8 12
Median (Full Range)
Unit of Measure: hours
2.5
(1 to 44)
3.7
(2 to 8)
2.8
(2 to 7)
12.Secondary Outcome
Title Part 1: Trough Concentration (Ctrough)
Hide Description Ctrough was derived from observed data.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 3 3 3
Median (Full Range)
Unit of Measure: μg/mL
23.1
(19.2 to 31.5)
61.3
(56.1 to 65)
130
(127 to 187)
92.4
(91.3 to 151)
13.Secondary Outcome
Title Part 2: Trough Concentration (Ctrough)
Hide Description Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose-Expansion): Basket Cohort Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 24 8 11
Median (Full Range)
Unit of Measure: μg/mL
84.1
(24 to 429)
90.1
(51 to 183)
101.7
(66 to 250)
14.Secondary Outcome
Title Part 1: Elimination Half-life (T½)
Hide Description Estimated using non-compartmental methods and actual time points.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Numbers reflects evaluable participants. Evaluable participants = T½ is only reported if at least three data points were available in the terminal phase, R2 in 0.85 or above and the time span between the first and the last data point for z covers at least 1.5 half-lives. Reference: V-QUAL-107812
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 3 1 1 1
Median (Full Range)
Unit of Measure: hours
179
(116 to 179)
137
(137 to 137)
193
(193 to 193)
170
(170 to 170)
15.Secondary Outcome
Title Part 2: Elimination Half-life (T½)
Hide Description Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose-Expansion): Basket Cohort Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 13 6 7
Median (Full Range)
Unit of Measure: hours
150
(87 to 217)
191
(103 to 208)
171
(116 to 204)
16.Secondary Outcome
Title Part 1: Clearance (CL)
Hide Description Estimated using non-compartmental methods and actual time points.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were determined for subjects in the 6 and 12 mg/kg cohorts. No samples from subjects in the 18 and 24 mg/kg cohorts were available for analysis.
Arm/Group Title 6 mg/kg 12 mg/kg 18 mg/kg 24 mg/kg
Hide Arm/Group Description:
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Overall Number of Participants Analyzed 1 1 0 0
Median (Full Range)
Unit of Measure: mL/h
0.3
(0.3 to 0.3)
0.2
(0.2 to 0.2)
17.Secondary Outcome
Title Part 2: Clearance (CL)
Hide Description Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time Frame From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 (Dose-Expansion): Basket Cohort Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Hide Arm/Group Description:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.

Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.

NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.

Overall Number of Participants Analyzed 7 1 2
Median (Full Range)
Unit of Measure: mL/h/kg
0.4
(0.2 to 0.5)
0.2
(0.2 to 0.2)
0.2
(0.2 to 0.2)
18.Secondary Outcome
Title Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
Hide Description

This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.

Objective Response (OR) is presented. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).

Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patients With Prior MET-targeting TKI Therapy (Basket Cohort) Patients Without Prior MET-targeting TKI Therapy (Basket Cohort)
Hide Arm/Group Description:
Patients in Basket Cohort, with prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Patients in Basket Cohort, without prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Overall Number of Participants Analyzed 5 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
19.Secondary Outcome
Title Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
Hide Description

This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.

Disease control rate (DCR) is presented. The DCR was defined as the percentage of patients who had BOR of confirmed CR or confirmed PR or SD (including unconfirmed CR/PR, provided 6 weeks minimum criteria for SD duration was met).

BOR = Best Overall Response. CR = Complete Response. PR = Partial Response. SD = Stable Disease.

Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patients With Prior MET-targeting TKI Therapy (Basket Cohort) Patients Without Prior MET-targeting TKI Therapy (Basket Cohort)
Hide Arm/Group Description:
Patients in Basket Cohort, with prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Patients in Basket Cohort, without prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Overall Number of Participants Analyzed 5 20
Measure Type: Count of Participants
Unit of Measure: Participants
2
  40.0%
8
  40.0%
Time Frame 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Dose-Escalation; Period 1: 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Hide Arm/Group Description

Patients received 6 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.

Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

Basket Cohort:

Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

NSCLC MET-Amplified Cohort:

Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:

NSCLC METex14del Cohort:

Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.

Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

All-Cause Mortality
Part 1: Dose-Escalation; Period 1: 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/25 (0.00%)      0/8 (0.00%)      3/12 (25.00%)    
Hide Serious Adverse Events
Part 1: Dose-Escalation; Period 1: 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      1/3 (33.33%)      0/3 (0.00%)      1/3 (33.33%)      8/25 (32.00%)      4/8 (50.00%)      6/12 (50.00%)    
Blood and lymphatic system disorders               
Febrile neutropenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders               
Intra-abdominal fluid collection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Nausea  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Colitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Rectal hemorrhage  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Small intestinal perforation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 1/12 (8.33%)  1
General disorders               
Generalized edema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Edema peripheral  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 0/12 (0.00%)  0
Hepatobiliary disorders               
Hepatitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 0/12 (0.00%)  0
Infections and infestations               
Pelvic abscess  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Pneumonia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 1/12 (8.33%)  1
Bacteraemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Bone abscess  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 0/12 (0.00%)  0
Septic shock  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 0/12 (0.00%)  0
Metabolism and nutrition disorders               
Hyperkalemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  2 0/8 (0.00%)  0 0/12 (0.00%)  0
Hypoalbuminemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Bone pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 1/12 (8.33%)  1
Pain in extremity  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders               
Cerebrovascular accident  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders               
Pleural effusion  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 1/12 (8.33%)  2
Pulmonary embolism  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 1/12 (8.33%)  3
Respiratory failure  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 1/12 (8.33%)  2
Vascular disorders               
Peripheral ischemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 1/8 (12.50%)  1 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Dose-Escalation; Period 1: 6 mg/kg Part 1: Dose-Escalation; Period 2: 12mg/kg Part 1: Dose-Escalation; Period 3:18mg/kg Part 1: Dose-Escalation; Period 4: 24 mg/kg Part 2: Dose-Expansion, Basket Cohort Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      23/25 (92.00%)      8/8 (100.00%)      12/12 (100.00%)    
Blood and lymphatic system disorders               
Anemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 6/25 (24.00%)  9 1/8 (12.50%)  1 1/12 (8.33%)  3
Ear and labyrinth disorders               
Ear pain  1  0/3 (0.00%)  0 2/3 (66.67%)  3 0/3 (0.00%)  0 1/3 (33.33%)  1 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Ear discomfort  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Ear hemorrhage  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders               
Nausea  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 6/25 (24.00%)  6 2/8 (25.00%)  2 2/12 (16.67%)  2
Constipation  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 5/25 (20.00%)  5 2/8 (25.00%)  2 2/12 (16.67%)  2
Abdominal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 5/25 (20.00%)  5 1/8 (12.50%)  2 1/12 (8.33%)  1
Dyspepsia  1  1/3 (33.33%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 2/8 (25.00%)  2 1/12 (8.33%)  2
Vomiting  1  1/3 (33.33%)  1 1/3 (33.33%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 2/8 (25.00%)  2 0/12 (0.00%)  0
Diarrhea  1  1/3 (33.33%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 0/8 (0.00%)  0 2/12 (16.67%)  2
Abdominal pain upper  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 1/8 (12.50%)  1 0/12 (0.00%)  0
Presbyesophagus  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Salivary gland enlargement  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Ascites  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
General disorders               
Edema peripheral  1  1/3 (33.33%)  1 1/3 (33.33%)  3 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 3/8 (37.50%)  6 7/12 (58.33%)  11
Fatigue  1  1/3 (33.33%)  1 1/3 (33.33%)  1 1/3 (33.33%)  1 1/3 (33.33%)  1 6/25 (24.00%)  7 1/8 (12.50%)  1 3/12 (25.00%)  3
Pyrexia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/25 (16.00%)  8 2/8 (25.00%)  2 1/12 (8.33%)  1
Asthenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 1/8 (12.50%)  1 1/12 (8.33%)  1
Early satiety  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Facial pain  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Feeling abnormal  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Infections and infestations               
Upper respiratory tract infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 1/8 (12.50%)  1 1/12 (8.33%)  1
Cystitis  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Injury, poisoning and procedural complications               
Infusion related reaction  1  0/3 (0.00%)  0 0/3 (0.00%)  0 2/3 (66.67%)  2 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Investigations               
Aspartate aminotransferase increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 3/8 (37.50%)  3 1/12 (8.33%)  1
Neutrophil count decreased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/25 (16.00%)  5 0/8 (0.00%)  0 0/12 (0.00%)  0
Blood creatine phosphokinase increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 2/8 (25.00%)  2 0/12 (0.00%)  0
Weight decreased  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 1/8 (12.50%)  2 0/12 (0.00%)  0
Alanine aminotransferase increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 1/8 (12.50%)  1 0/12 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite  1  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 6/25 (24.00%)  6 0/8 (0.00%)  0 3/12 (25.00%)  4
Hypoalbuminemia  1  1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 5/25 (20.00%)  7 1/8 (12.50%)  1 1/12 (8.33%)  2
Hypokalemia  1  2/3 (66.67%)  2 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/25 (8.00%)  6 0/8 (0.00%)  0 0/12 (0.00%)  0
Hypomagnesemia  1  1/3 (33.33%)  1 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Hyponatremia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/25 (12.00%)  5 0/8 (0.00%)  0 1/12 (8.33%)  1
Dehydration  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Back pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/25 (12.00%)  3 3/8 (37.50%)  3 0/12 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Tumor pain  1  1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders               
Headache  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 3/8 (37.50%)  3 0/12 (0.00%)  0
Somnolence  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 2/8 (25.00%)  2 0/12 (0.00%)  0
Dysgeusia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 0/8 (0.00%)  0 2/12 (16.67%)  2
Dizziness  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Cognitive disorder  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Psychiatric disorders               
Insomnia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Renal and urinary disorders               
Urinary incontinence  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Reproductive system and breast disorders               
Pelvic discomfort  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Cough  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  4 1/8 (12.50%)  1 5/12 (41.67%)  6
Dyspnea  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 1/25 (4.00%)  1 1/8 (12.50%)  1 2/12 (16.67%)  3
Pleural effusion  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Oropharyngeal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 2/25 (8.00%)  2 0/8 (0.00%)  0 0/12 (0.00%)  0
Respiratory tract congestion  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders               
Pruritus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/25 (8.00%)  2 1/8 (12.50%)  2 0/12 (0.00%)  0
Vascular disorders               
Flushing  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
Hypertension  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/25 (0.00%)  0 0/8 (0.00%)  0 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Symphogen AS
Phone: 0045 45265050
EMail: info@symphogen.com
Layout table for additonal information
Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02648724    
Other Study ID Numbers: Sym015-01
2016-003912-11 ( EudraCT Number )
First Submitted: January 4, 2016
First Posted: January 7, 2016
Results First Submitted: December 21, 2021
Results First Posted: June 22, 2022
Last Update Posted: June 22, 2022