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

NCT02630186 | Terminated Phase 1 Results

• 1 other identifier: CO-1686-032
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The primary purpose of the Phase 1 portion of the study is to observe the safety of the combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients. The primary purpose of the Phase 2 portion of the study is to evaluate the safety and anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for the combination determined in Phase 1, in patients with EGFR-mutant NSCLC.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (8)

• Number of Treatment-emergent Adverse Events, as Assessed by NCI CTCAE v4.03

  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.

  Continuously, up to approximately 18.5 months

• Maximum Concentration (Cmax) of Rociletinib and Its Metabolites

  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.

  Treatment Day 1 and Day 15

• Time to Maximum Concentration (Tmax) for Rociletinib and Rociletinib Metabolites

  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.

  Treatment Day 1 and Day 15

• Minimum Concentration (Cmin) of Rociletinib and Metabolites

  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.

  Approximately every 6 weeks up to 24 months

• Area Under the Curve (AUC) of Rociletinib and Rociletinib Metabolites

  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.

  Treatment Day 1 and Day 8

• Maximum Concentration (Cmax) of MPDL3280A

  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.

  Cycle 1 Day 1

• Minimum Concentration (Cmin) of MPDL3280A

  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.

  Approximately every 6 weeks up to 24 months

• Objective Response Rate Per RECIST v1.1 in Phase 2

  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.

  Approximately every 6-9 weeks

Secondary Outcomes (5)

• Objective Response Rate Per Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2

  Approximately every 6-9 weeks, up to 24 months

• Duration of Response Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2

  Approximately every 6-9 weeks, up to 24 months

• Progression-free Survival Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2

  Approximately every 6-9 weeks, up to 24 months

• Number of Patients Alive at Study Termination

  Up to approximately 18.5 months

• Longitudinal Changes in Blood Based Biomarkers (eg, Mutations in EGFR) in ctDNA

  Blood samples will be collected from each patient approximately every 3 weeks, up to 24 months

Study Arms (1)

Single Arm Rociletinib and MPDL3280A

EXPERIMENTAL

Specific doses of rociletinib, taken continuously BID, will be administered in combination with a fixed dose of MPDL3280A, given intravenously on Day 1 of each 21-day cycle.

Drug: Rociletinib; Drug: MPDL3280A

Interventions

Rociletinib DRUG

A novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC.

Also known as: CO-1686

Single Arm Rociletinib and MPDL3280A

MPDL3280A DRUG

A human IgG1 monoclonal antibody administered intravenously (IV)

Also known as: atezolizumab

Single Arm Rociletinib and MPDL3280A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status of 0 or 1
• Adequate hematological and biological function, confirmed by defined laboratory values
• Histologically or cytologically documented metastatic or unresectable, locally advanced or metastatic NSCLC, with one or more activating EGFR mutation (eg, G719X, exon 19 deletion, L858R, L861Q) and absence of exon 20 insertion
• Measurable disease as defined by RECIST v1.1
• Biopsy of tumor tissue for central evaluation, within 60 days prior to the first day of study treatment
• For Phase 1 and Phase 2 Group B, progression after prior 1st or 2nd generation EGFR TKI (eg, erlotinib, gefitinib, afatinib). Previous chemotherapy for NSCLC is allowed.
• For Phase 2 Group A, EGFR TKI treatment-naïve and chemotherapy-naïve

You may not qualify if:

• Unresolved toxicities from prior therapy
• Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases
• Previous treatment with rociletinib or MPDL3280A, or other 3rd generation EGFR TKI (eg, AZD-9291, HM61713), or PD 1 axis targeted therapy (eg, anti PD 1 or anti-PD L1)
• Prior treatment with CD137 agonists or other immune checkpoint blockade therapies, including anti-CTLA-4 therapeutic antibodies
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (bisphosphonate use for prevention of skeletal events allowed)
• Known hypersensitivity to any component of the MPDL3280A or rociletinib formulations or history or hypersensitivity to chimeric humanized antibodies or fusion proteins
• History of autoimmune disease
• History of prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation
• Treatment with systemic immunosuppressive medications within 2 weeks prior to first day of study treatment (inhaled corticosteroids and mineralocorticoids allowed)
• Live attenuated vaccine within 4 weeks prior to first day of study treatment
• Active tuberculosis, active hepatitis, or positive HIV status
• Class II to IV heart failure as defined by the New York Heart Association functional classification system
• Untreated or uncontrolled cardiovascular disease or other symptomatic cardiac dysfunction
• QTCF \> 450 ms, inability to measure QT interval on ECG, personal or family history of long QT syndrome, requirement for medications that have the potential to prolong the QT interval

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of California at Los Angeles

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

rociletinib; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Elizabeth Bradley
• Organization: Clovis Oncology, Inc.

ebradley@clovisoncology.com

1-415-409-5495

Study Officials

• Lindsey Rolfe, MD

  Clovis Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2015
• First Posted: December 15, 2015
• Study Start: February 24, 2016
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: July 5, 2019
• Results First Posted: July 5, 2019

Record last verified: 2019-06

Locations

US (1)