ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 4 for:    LY2812176
Previous Study | Return to List | Next Study

A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors

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: NCT01457417
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : September 28, 2016
Last Update Posted : September 28, 2016
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Multiple Myeloma
Solid Tumors
Non-Small Cell Lung Cancer
Intervention Drug: DKN-01
Enrollment 32
Recruitment Details Eight sites in the United States participated in the study and 7 of them enrolled patients. The Date of First Enrollment was 16 Jan 2012, and the Date of Last Completed was 06 Dec 2013.
Pre-assignment Details Part A enrolled patients with histologically or cytologically confirmed multiple myeloma or advanced solid tumors. A dose escalation procedure was followed. Part B enrolled patients with non-small cell lung cancer. Following screening (up to 28 days prior to first treatment) if entry criterion was met, patients were eligible for enrollment.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Period Title: Overall Study
Started 3 3 4 3 19
Completed 3 3 4 3 19
Not Completed 0 0 0 0 0
Arm/Group Title 75 Milligram (mg) DKN-01 Part A 150 mg DKN-01 Part A 300 mg DKN-01 Part A 600 mg DKN-01 Part A 300 mg DKN-01 Part B Total
Hide Arm/Group Description DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. Total of all reporting groups
Overall Number of Baseline Participants 3 3 4 3 19 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 4 participants 3 participants 19 participants 32 participants
57.7  (7.77) 66.3  (8.62) 65.0  (19.20) 68.3  (8.96) 65.4  (9.25) 65.0  (10.29)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 4 participants 3 participants 19 participants 32 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
 100.0%
1
  33.3%
2
  50.0%
1
  33.3%
10
  52.6%
17
  53.1%
>=65 years
0
   0.0%
2
  66.7%
2
  50.0%
2
  66.7%
9
  47.4%
15
  46.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 4 participants 3 participants 19 participants 32 participants
Female
1
  33.3%
3
 100.0%
4
 100.0%
1
  33.3%
9
  47.4%
18
  56.3%
Male
2
  66.7%
0
   0.0%
0
   0.0%
2
  66.7%
10
  52.6%
14
  43.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 4 participants 3 participants 19 participants 32 participants
3 3 4 3 19 32
1.Primary Outcome
Title Summary of Total Adverse Events (AE)
Hide Description Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B.
Time Frame Baseline to study completion (approximately 3 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W) Total
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Total across all treatment groups
Overall Number of Participants Analyzed 3 3 4 3 19 32
Measure Type: Number
Unit of Measure: Events
Total AEs 39 58 35 11 87 230
Total TEAEs 39 58 35 9 87 228
Total SAEs 2 7 3 0 11 23
Total DLTs 0 0 0 0 0 0
2.Primary Outcome
Title Summary of Patients With Adverse Events (AE)
Hide Description Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category.
Time Frame Baseline to study completion (approximately 3 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W) Total
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Total across all treatment groups
Overall Number of Participants Analyzed 3 3 4 3 19 32
Measure Type: Number
Unit of Measure: Patients
At Least One AE 3 3 4 3 16 29
At Least One TEAE 3 3 4 3 16 29
At Least One SAE 1 2 1 0 7 11
Retracted SAE 1 2 0 0 2 5
SAE related to study drug 0 0 0 0 0 0
TEAE of Maximum CTCAE - Grade 1 Mild 0 0 0 0 0 0
TEAE of Maximum CTCAE - Grade 2 Moderate 2 1 1 3 6 13
TEAE of Maximum CTCAE - Grade 3 Severe 0 2 3 0 9 14
TEAE of Maximum CTCAE - Grade 4 Life Threatening 1 0 0 0 0 1
TEAE of Maximum CTCAE - Grade 5 Death 0 0 0 0 1 1
TEAE Grade ≥ 3 assessed as study drug related 0 0 0 0 0 0
TEAE of Maximum Relationship - Related 1 2 3 1 8 15
TEAE of Maximum Relationship - Not Related 2 1 1 2 8 14
At Least One TEAE Leading to Drug Withdrawal 0 1 0 0 3 4
At Least One TEAE Leading to Study Discontinuation 0 0 0 0 0 0
At Least One TEAE with Outcome of Death 0 0 0 0 1 1
3.Primary Outcome
Title Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
Hide Description For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
Time Frame Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients with advanced NSCLC receiving the study drug at 300 mg every 2 weeks in Part B
Arm/Group Title 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: months
2.2
(1.5 to 2.9)
4.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Hide Description Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups.
Time Frame Cycle 1 Day 1 (first dose, all groups)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of study treatment during Part A or Part B of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 3 3 18
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
1942552.08830  (780226.768012) 4381685.27190  (402701.016054) 10860453.92050  (2319628.494223) 18103276.11133  (1250736.327819) 18398867.35928  (5107540.116369)
5.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Hide Description Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 day 22 included only QW dosing groups.
Time Frame Cycle 1 Day 22 (Fourth Dose for QW)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of study treatment during Part A study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 3 0 0
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
5663382.27007  (3919446.471337) 15815320.60770  (5614032.150398) 25639949.52467  (4567585.003954)
6.Secondary Outcome
Title Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Hide Description Peak DKN-01 serum concentration (Cmax) after the first and fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups.
Time Frame Cycle 1 Day 1 (first dose, all groups)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of study treatment during Part A or Part B of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 3 3 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
22756.09897  (7665.992335) 47838.87113  (4193.154016) 130105.94600  (25705.162094) 183063.33233  (34635.447386) 119837.93546  (43565.776017)
7.Secondary Outcome
Title Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Hide Description Peak DKN-01 serum concentration (Cmax) after the fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 day 22 included only QW dosing groups.
Time Frame Cycle 1 Day 22 (Fourth dose for QW groups)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of study treatment during Part A of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 3 0 0
Mean (Standard Deviation)
Unit of Measure: ng/mL
43203.11520  (25085.681036) 105148.29720  (29480.395189) 224382.14533  (28438.209780)
8.Secondary Outcome
Title Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
Hide Description For both Parts A and B. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (i.e, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
Time Frame Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of study treatment during Part A or Part B of the study.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 4 3 19
Median (95% Confidence Interval)
Unit of Measure: Months
3.4
(2.2 to 4.7)
2.4
(1.7 to 3.3)
2.1
(1.5 to 2.2)
2.1
(2.1 to 2.2)
2.2
(1.5 to 2.9)
9.Secondary Outcome
Title Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC
Hide Description For Part B only. OS was defined as the time from the date of signed informed consent to the date of death from any cause. For patients who were still alive as of the data cut-off date, OS time was censored on the date of the patient’s last contact (last contact for patients in post-discontinuation was the last date of contact in long-term follow-up eCRF).
Time Frame Time from the date of signed informed consent to the date of death from any cause
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For patients who are still alive as of the data cut-off date, OS time will be censored on the date of the patient’s last contact (last contact for patients in post-discontinuation = last Date of Contact in Long Term Follow-up eCRF).
Arm/Group Title 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: Months
6.6
(4.1 to 10.1)
10.Secondary Outcome
Title Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
Hide Description For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR)
Time Frame Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients with NSCLC who received at least one dose of study treatment during Part A or Part B of the study. One Patients from the 300 mg QW treatment group, and two patients from 300 mg Q2W treatment group did not have assessments performed after Baseline.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 3 3 3 3 17
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants
0
(0 to 70.8)
0
(0 to 70.8)
0
(0 to 60.2)
0
(0 to 70.8)
1
(.1 to 26.0)
11.Secondary Outcome
Title Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
Hide Description FAS : For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR)
Time Frame Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS : NSCLC - All patients with NSCLC who received at least one dose of study treatment during Part A or Part B of the study. Two patients in treatment group 300 mg Q2W did not have assessments performed after Baseline.
Arm/Group Title 75 Milligram (mg) DKN-01 Part A (QW) 150 mg DKN-01 Part A (QW) 300 mg DKN-01 Part A (QW) 600 mg DKN-01 Part A (Q2W) 300 mg DKN-01 Part B (Q2W)
Hide Arm/Group Description:
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.
Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
Overall Number of Participants Analyzed 2 1 0 2 17
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
0
(0.0 to 84.2)
0
(0.0 to 97.5)
0
(0.0 to 84.2)
1
(0.1 to 26.0)
Time Frame Entirety of the study. 1 year, 3 months.
Adverse Event Reporting Description Safety analyses were based on the full analysis set (FAS), which was defined as all patients who received at least one dose of study treatment during Part A or Part B of the study. Assessments up to 30 days after the date of last dose of study medication (for serious adverse events and unresolved study drug-related AEs) were included.
 
Arm/Group Title 75 Milligram (mg) DKN-01 Part A 150 mg DKN-01 Part A 300 mg DKN-01 Part A 600 mg DKN-01 Part A 300 mg DKN-01 Part B
Hide Arm/Group Description DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) was met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.
All-Cause Mortality
75 Milligram (mg) DKN-01 Part A 150 mg DKN-01 Part A 300 mg DKN-01 Part A 600 mg DKN-01 Part A 300 mg DKN-01 Part B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
75 Milligram (mg) DKN-01 Part A 150 mg DKN-01 Part A 300 mg DKN-01 Part A 600 mg DKN-01 Part A 300 mg DKN-01 Part B
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%)      2/3 (66.67%)      1/4 (25.00%)      0/3 (0.00%)      6/19 (31.58%)    
Cardiac disorders           
CARDIO-RESPIRATORY ARREST  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 0/19 (0.00%)  0
ATRIAL FIBRILLATION * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 1/19 (5.26%)  1
PERICARDIAL EFFUSION * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/19 (0.00%)  0
Gastrointestinal disorders           
ASCITES * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/4 (0.00%)  0 0/3 (0.00%)  0 0/19 (0.00%)  0
NAUSEA * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/4 (25.00%)  1 0/3 (0.00%)  0 0/19 (0.00%)  0
VOMITING * 1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/4 (25.00%)  1 0/3 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations           
PNEUMONIA * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 3/19 (15.79%)  3
Respiratory, thoracic and mediastinal disorders           
PLEURAL EFFUSION * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/19 (5.26%)  1
PULMONARY EMBOLISM * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/19 (5.26%)  1
RESPIRATORY FAILURE * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/19 (5.26%)  1
Surgical and medical procedures           
PAIN MANAGEMENT * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/4 (25.00%)  1 0/3 (0.00%)  0 0/19 (0.00%)  0
Vascular disorders           
SUPERIOR VENA CAVA SYNDROME * 1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/3 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
75 Milligram (mg) DKN-01 Part A 150 mg DKN-01 Part A 300 mg DKN-01 Part A 600 mg DKN-01 Part A 300 mg DKN-01 Part B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      4/4 (100.00%)      3/3 (100.00%)      16/19 (84.21%)    
Gastrointestinal disorders           
NAUSEA * 1  1/3 (33.33%)  2/3 (66.67%)  2/4 (50.00%)  1/3 (33.33%)  4/19 (21.05%) 
VOMITTING * 1  1/3 (33.33%)  2/3 (66.67%)  1/4 (25.00%)  1/3 (33.33%)  2/19 (10.53%) 
CONSTIPATION * 1  2/3 (66.67%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  2/19 (10.53%) 
DYSPHAGIA * 1  1/3 (33.33%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  1/19 (5.26%) 
General disorders           
FATIGUE * 1  0/3 (0.00%)  2/3 (66.67%)  3/4 (75.00%)  0/3 (0.00%)  4/19 (21.05%) 
ASTHENIA * 1  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  1/19 (5.26%) 
Metabolism and nutrition disorders           
DECREASED APPETITE * 1  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  4/19 (21.05%) 
HYPOKALAEMIA * 1  0/3 (0.00%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  2/19 (10.53%) 
Respiratory, thoracic and mediastinal disorders           
DYSPNOEA * 1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  6/19 (31.58%) 
PNEUMONIA * 1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/19 (15.79%) 
PRODUCTIVE COUGH * 1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/19 (15.79%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Publication of the results shall not be made before the publication by Sponsor. If there is no multi-site publication within 18 months after the Study completion/termination at all sites, the Site shall have the right to publish its results. Prior to submitting to public release the Sponsor has 60 days from receipt to review and comment. The Site shall, upon Sponsor's request, further delay publication/presentation for up to 120 days to allow Sponsor to protect its interests.
Results Point of Contact
Name/Title: Cynthia Sirard, MD
Organization: Healthcare Pharmaceuticals, Inc
Phone: 617-714-0357
Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01457417     History of Changes
Other Study ID Numbers: P100
DEK-DKK1-P100 ( Other Identifier: Healthcare Pharmaceuticals )
LY2812176 ( Other Identifier: Healthcare Pharmaceuticals )
First Submitted: October 18, 2011
First Posted: October 24, 2011
Results First Submitted: January 13, 2015
Results First Posted: September 28, 2016
Last Update Posted: September 28, 2016