Clinical Trial: NCT03337698 - My Cancer Genome

NCT03337698

Description:

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in patients with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: the first-line (1L) cohort will consist of patients who have not received any systemic therapy for their disease and the second-line (2L) cohort will consist of patients who progressed during or after receiving a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor treatment. In each cohort, eligible patients will be assigned to one of several treatment arms.

Related Conditions:

Non-Small Cell Lung Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03337698

Trial Eligibility

Document

Title

Brief Title: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)

Clinical Trial IDs

ORG STUDY ID: BO39610
SECONDARY ID: 2017-001267-21
NCT ID: NCT03337698

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug	Synonyms	Arms
Atezolizumab		Stage 1: Cohort 1: Atezolizumab
Cobimetinib		Stage 1: Cohort 1: Atezolizumab + Cobimetinib
RO6958688		Stage 1: Cohort 1: Atezolizumab + RO6958688
Docetaxel		Stage 1: Cohort 2: Atezolizumab + Docetaxel
CPI-444		Stage 1: Cohort 2: Atezolizumab + CPI-444
Pemetrexed		Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Carboplatin		Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Gemcitabine		Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Linagliptin		Stage 2: Cohort 2: Atezolizumab + Linagliptin
Tocilizumab		Stage 1: Cohort 1: Atezolizumab + RO6958688
Ipatasertib		Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Bevacizumab		Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Sacituzumab Govitecan		Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Evolocumab		Stage 1: Cohort 2: Atezolizumab + Evolocumab

Purpose

Trial Arms

Name	Type	Description	Interventions
Stage 1: Cohort 1: Atezolizumab	Active Comparator	Participants in the Atezolizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.	Atezolizumab
Stage 1: Cohort 1: Atezolizumab + Cobimetinib	Experimental	Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab Cobimetinib
Stage 1: Cohort 1: Atezolizumab + RO6958688	Experimental	Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab RO6958688 Tocilizumab
Stage 1: Cohort 2: Docetaxel	Active Comparator	Participants in the Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or disease progression. Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6958688 or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Docetaxel
Stage 1: Cohort 2: Atezolizumab + Cobimetinib	Experimental	Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab Cobimetinib
Stage 1: Cohort 2: Atezolizumab + CPI-444	Experimental	Participants in the Atezolizumab + CPI-444 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab CPI-444
Stage 1: Cohort 2: Atezolizumab + RO6958688	Experimental	Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab RO6958688 Tocilizumab
Stage 1: Cohort 2: Atezolizumab + Ipatasertib	Experimental	Participants in the Atezolizumab + Ipatasertib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab Ipatasertib
Stage 1: Cohort 2: Atezolizumab + Docetaxel	Experimental	Participants in Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab Docetaxel
Stage 1: Cohort 2: Atezolizumab + Bevacizumab	Experimental	Participants in Atezolizumab + Bevacizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Atezolizumab Bevacizumab
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin	Experimental	Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Pemetrexed Carboplatin
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin	Experimental	Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Carboplatin Gemcitabine
Stage 2: Cohort 2: Atezolizumab + RO6958688	Experimental	Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab RO6958688 Tocilizumab
Stage 2: Cohort 2: Atezolizumab + Docetaxel	Experimental	Participants in the Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who have received treatment with Atezolizumab + Docetaxel in Stage 1 will not receive this treatment in Stage 2.	Atezolizumab Docetaxel
Stage 2: Cohort 2: Atezolizumab + Linagliptin	Experimental	Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Linagliptin
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan	Experimental	Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Sacituzumab Govitecan
Stage 1: Cohort 2: Atezolizumab + bevacizumab + Radiotherapy	Experimental	Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Bevacizumab
Stage 1: Cohort 2: Atezolizumab + Evolocumab	Experimental	Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.	Atezolizumab Evolocumab

Eligibility Criteria

        General Inclusion Criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1

          -  Life expectancy greater than or equal to 3 months

          -  Histologically or cytologically confirmed metastatic, non-squamous or squamous
             Non-Small Cell Lung Cancer (NSCLC)

          -  Measurable disease (at least one target lesion)

          -  Adequate hematologic and end-organ function

          -  Tumor accessible for biopsy

          -  Availability of peripheral blood for next-generation sequencing (NGS) circulating
             tumor deoxyribonucleic acid (ctDNA) testing.

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive measures and agreement to refrain from
             donating eggs as outlined for each specific treatment arm

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures, and agreement to refrain from donating sperm, as outlined for
             each specific treatment arm

        Inclusion Criteria for Cohort 1

          -  No prior systemic therapy for metastatic NSCLC

          -  High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) >= 50%

        Inclusion Criteria for Cohort 2

        - Disease progression during or following treatment for metastatic or locally advanced,
        inoperable NSCLC

        Exclusion Criteria

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases

          -  History of leptomeningeal disease

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography scan

          -  History of malignancy other than NSCLC within 2 years prior to screening

          -  Active tuberculosis

          -  Severe infection within 4 weeks prior to initiation of study treatment

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of Participants with Objective Response
Time Frame:	Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Progression Free Survival (PFS)
Time Frame:	Randomization to the first occurrence of disease progression or death from any cause (up to approximately 7 years)
Safety Issue:
Description:

Measure:	Overall Survival After Randomization
Time Frame:	Randomization to death from any cause (up to approximately 7 years)
Safety Issue:
Description:

Measure:	Percentage of Participants Who Are Alive at Month 6 and at Month 12
Time Frame:	Month 6, Month 12
Safety Issue:
Description:

Measure:	Duration of Response
Time Frame:	First occurrence of a documented objective response to disease progression or death (up to approximately 7 years)
Safety Issue:
Description:

Measure:	Disease Control
Time Frame:	Randomization to the first occurrence of disease progression or death from any cause (up to approximately 7 years)
Safety Issue:
Description:

Measure:	Percentage of Participants with Adverse Events
Time Frame:	Baseline through the end of the study (approximately 7 years)
Safety Issue:
Description:

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Hoffmann-La Roche

Last Updated

August 27, 2021

Clinical Trials /

A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)