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

NCT ID: NCT02630186

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-24
• Study Completion Date: 2017-09-05

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.

Detailed Description

This is a Phase 1b/2, open-label, non-randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with MPDL3280A.

Phase 1: This will be the dose finding phase of the study. Patients will be enrolled to available Dosing Cohort. Patients who have progressed after prior first- or second-generation EGFR TKI, regardless of T790M mutation status, will be enrolled.

Phase 2: Patients will be enrolled into 2 groups. Group A will enroll eligible first-line patients who are EGFR TKI treatment-naïve and chemotherapy-naïve. Group B will enroll eligible patients who have progressed after prior first- or second-generation EGFR TKI, regardless of T790M mutation status.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm Rociletinib and MPDL3280A

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.

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

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

MPDL3280A

Intervention Type: DRUG

A human IgG1 monoclonal antibody administered intravenously (IV)

Interventions

Rociletinib

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

Intervention Type: DRUG

MPDL3280A

A human IgG1 monoclonal antibody administered intravenously (IV)

Intervention Type: DRUG

Other Intervention Names

CO-1686; atezolizumab

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan (history of radiation pneumonitis in radiation field may be allowed)
• Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindsey Rolfe, MD

Role: STUDY_DIRECTOR

Clovis Oncology, Inc.

Locations

University of California at Los Angeles

Santa Monica, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CO-1686-032

Identifier Type: -

Identifier Source: org_study_id