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A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC

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: NCT02630186
Recruitment Status : Terminated (The study terminated before Phase 1 was completed. This study was reprioritized within the rociletinib development program.)
First Posted : December 15, 2015
Results First Posted : July 4, 2019
Last Update Posted : July 4, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Rociletinib
Drug: MPDL3280A
Enrollment 3
Recruitment Details Three patients were enrolled at a single center in the United States.
Pre-assignment Details The Dose Finding Phase included a 7 day Run in Period of rociletinib monotherapy, at the Dosing Cohort-defined dose level, prior to the initiation of combination treatment.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Period Title: Overall Study
Started 3
Completed 2
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
<=18 years
0
   0.0%
Between 18 and 65 years
1
  33.3%
>=65 years
2
  66.7%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants
66
(54 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
3
 100.0%
Male
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
  33.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
2
  66.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants
3
1.Primary Outcome
Title Number of Treatment-emergent Adverse Events, as Assessed by NCI CTCAE v4.03
Hide Description The safety analyses will be performed using the safety population. Safety data analysis will be conducted on all patients receiving at least one dose of rociletinib or MPDL3280A.
Time Frame Continuously, up to approximately 18.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled in the study.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Treatment emergent adverse events
31
2.Primary Outcome
Title Maximum Concentration (Cmax) of Rociletinib and Its Metabolites
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmax will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Treatment Day 1 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Time to Maximum Concentration (Tmax) for Rociletinib and Rociletinib Metabolites
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Tmax will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Treatment Day 1 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Primary Outcome
Title Minimum Concentration (Cmin) of Rociletinib and Metabolites
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmin will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Approximately every 6 weeks up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Primary Outcome
Title Area Under the Curve (AUC) of Rociletinib and Rociletinib Metabolites
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. AUC0 24 will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Treatment Day 1 and Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK sample collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title Maximum Concentration (Cmax) of MPDL3280A
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmax, for MPDL3280A will be assessed using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Primary Outcome
Title Minimum Concentration (Cmin) of MPDL3280A
Hide Description Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmin for MPDL3280A will be assessed using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.
Time Frame Approximately every 6 weeks up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Primary Outcome
Title Objective Response Rate Per RECIST v1.1 in Phase 2
Hide Description

To determine the efficacy of the combination of rociletinib and MPDL3280A based on overall response rate per RECIST v1.1 in the following groups of patients:

  • Group A: Patients with EGFRm advanced or metastatic NSCLC who have not previously received an EGFR TKI or chemotherapy.
  • Group B: Patients with EGFRm advanced or metastatic NSCLC who have progressed on a prior EGFR TKI.
Time Frame Approximately every 6-9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Objective Response Rate Per Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
Hide Description

Conventional response criteria may not be adequate to characterize the antitumor activity of immunotherapeutic agents like MPDL3280A, which can produce delayed responses that may be preceded by initial apparent radiological progression, including the appearance of new lesions. Therefore, modified response criteria have been developed that account for the possible appearance of new lesions and allow radiological progression to be confirmed at a subsequent assessment. In this protocol, patients will be permitted to continue study treatment even after modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progressive disease are met if the benefit-risk ratio is judged to be favorable.

These modified criteria are derived from RECIST version 1.1 (v1.1) conventions and immune related response criteria (irRC).

Time Frame Approximately every 6-9 weeks, up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Duration of Response Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
Hide Description

Conventional response criteria may not be adequate to characterize the antitumor activity of immunotherapeutic agents like MPDL3280A, which can produce delayed responses that may be preceded by initial apparent radiological progression, including the appearance of new lesions. Therefore, modified response criteria have been developed that account for the possible appearance of new lesions and allow radiological progression to be confirmed at a subsequent assessment. In this protocol, patients will be permitted to continue study treatment even after modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progressive disease are met if the benefit-risk ratio is judged to be favorable.

These modified criteria are derived from RECIST version 1.1 (v1.1) conventions and immune related response criteria (irRC).

Time Frame Approximately every 6-9 weeks, up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Progression-free Survival Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
Hide Description

Conventional response criteria may not be adequate to characterize the antitumor activity of immunotherapeutic agents like MPDL3280A, which can produce delayed responses that may be preceded by initial apparent radiological progression, including the appearance of new lesions. Therefore, modified response criteria have been developed that account for the possible appearance of new lesions and allow radiological progression to be confirmed at a subsequent assessment. In this protocol, patients will be permitted to continue study treatment even after modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progressive disease are met if the benefit-risk ratio is judged to be favorable.

These modified criteria are derived from RECIST version 1.1 (v1.1) conventions and immune related response criteria (irRC).

Time Frame Approximately every 6-9 weeks, up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Number of Patients Alive at Study Termination
Hide Description Patients who received the combination of rociletinib and MPDL3280A alive at the termination of this study.
Time Frame Up to approximately 18.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Count of the number of enrolled patients alive at study termination.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
2
13.Secondary Outcome
Title Longitudinal Changes in Blood Based Biomarkers (eg, Mutations in EGFR) in ctDNA
Hide Description Tumor tissue, plasma, and blood specimens will be used for pharmacodynamic assessment of rociletinib and/or MPDL3280A activity, to evaluate the concordance of mutant EGFR detection between tissue and plasma, and to explore biomarkers that may be predictive of response or resistance to rociletinib and/or MPDL3280A. Biomarkers and changes in biomarker status will be investigated for associations with rociletinib and/or MPDL3280A exposure, safety, and clinical activity. Given the limited sample size, no formal statistical analysis is planned.
Time Frame Blood samples will be collected from each patient approximately every 3 weeks, up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the small number of patients enrolled and small number of samples collected as a result of early termination of the study, these analyses were not conducted.
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description:
Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug.
Adverse Event Reporting Description One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
 
Arm/Group Title Single Arm Rociletinib and MPDL3280A in Combination
Hide Arm/Group Description Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
All-Cause Mortality
Single Arm Rociletinib and MPDL3280A in Combination
Affected / at Risk (%)
Total   0/3 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Single Arm Rociletinib and MPDL3280A in Combination
Affected / at Risk (%) # Events
Total   1/3 (33.33%)    
Gastrointestinal disorders   
Pancreatitis  1  1/3 (33.33%)  1
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Single Arm Rociletinib and MPDL3280A in Combination
Affected / at Risk (%) # Events
Total   3/3 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  1/3 (33.33%)  1
Ear and labyrinth disorders   
Eustachian tube dysfunction  1  1/3 (33.33%)  1
Bilateral hearing loss  1  1/3 (33.33%)  1
Eye disorders   
Cataracts  1  1/3 (33.33%)  1
Gastrointestinal disorders   
Nausea  1  2/3 (66.67%)  2
Diarrhea  1  3/3 (100.00%)  3
Gastroesophageal reflux disease  1  1/3 (33.33%)  1
Stomach Pain  1  1/3 (33.33%)  2
Epigastric pain  1  1/3 (33.33%)  1
General disorders   
Fatigue  1  1/3 (33.33%)  1
Swelling finger  1  1/3 (33.33%)  1
Infections and infestations   
Cellulitis  1  1/3 (33.33%)  1
Urinary tract infection  1  1/3 (33.33%)  2
Herpes virus reactivation  1  1/3 (33.33%)  1
Investigations   
Increased Blood Sugar  1  1/3 (33.33%)  1
Stomach Pain  1  1/3 (33.33%)  1
Weight decreased  1  1/3 (33.33%)  1
Prolonged QTc interval  1  1/3 (33.33%)  2
Intermittent epigastric discomfort  1  1/3 (33.33%)  1
Elevated aspartate aminotransferase  1  1/3 (33.33%)  1
Elevated alanine aminotransferase  1  1/3 (33.33%)  1
Elevated blood alkaline phosphatase  1  1/3 (33.33%)  1
Metabolism and nutrition disorders   
Hyperglycemia  1  1/3 (33.33%)  3
Hyponatremia  1  1/3 (33.33%)  1
Anorexia  1  1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders   
Muscle Cramps  1  2/3 (66.67%)  2
Nervous system disorders   
Headache  1  1/3 (33.33%)  2
Renal and urinary disorders   
Dysuria  1  1/3 (33.33%)  1
Skin and subcutaneous tissue disorders   
Ecchymosis  1  1/3 (33.33%)  1
Firm raised lesion, dorsum of left foot  1  1/3 (33.33%)  1
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
This study was terminated early which lead to small number of subjects analyzed. The study did not reach the target number of participants needed to achieve target power and statistically reliable results.
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: Elizabeth Bradley
Organization: Clovis Oncology, Inc.
Phone: 1-415-409-5495
EMail: ebradley@clovisoncology.com
Layout table for additonal information
Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02630186     History of Changes
Other Study ID Numbers: CO-1686-032
First Submitted: December 2, 2015
First Posted: December 15, 2015
Results First Submitted: November 1, 2018
Results First Posted: July 4, 2019
Last Update Posted: July 4, 2019