Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Atezolizumab

Immunoglobulins

Tyrosine Kinase Inhibitors

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

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.

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

Rociletinib

A human IgG1 monoclonal antibody administered intravenously (IV)

MPDL3280A

Lindsey Rolfe, MD

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.

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.

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

A Phase 1b/2 Study of the Safety and Efficacy of Rociletinib (CO-1686) Administered in Combination With MPDL3280A in Patients With Activating EGFR Mutation-positive (EGFRm) Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

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.

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.

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.

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.

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.

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.

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.

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.

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).

Patients who received the combination of rociletinib and MPDL3280A alive at the termination of this study.

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.

Genentech, Inc.

Clovis Oncology, Inc.

One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.

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).

Single Arm Rociletinib and MPDL3280A in Combination

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

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.

Elizabeth Bradley

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

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.

Maximum Concentration (Cmax) of Rociletinib and Its Metabolites

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

Minimum Concentration (Cmin) of Rociletinib and Metabolites

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.

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

Maximum Concentration (Cmax) of MPDL3280A

Minimum Concentration (Cmin) of MPDL3280A

Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.

Objective Response Rate Per RECIST v1.1 in Phase 2

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

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

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

Count of the number of enrolled patients alive at study termination.

Number of Patients Alive at Study Termination

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.

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

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