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

NCT03337698 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: BO396102017-001267-21
• Study Type: interventional
• Target: 314
• Locations: 7 countries
• Sites: 29

Brief Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Objective Response

  Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)

• Overall Survival After Randomization

  Randomization to death from any cause (up to approximately 8 years)

• Percentage of Participants Who Are Alive at Month 6 and at Month 12

  Month 6, Month 12

• Duration of Response

  First occurrence of a documented objective response to disease progression or death (up to approximately 8 years)

• Disease Control

  Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)

Study Arms (23)

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.

Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: RO6958688; Drug: 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.

Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: RO6958688; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: Pemetrexed; Drug: 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.

Drug: Atezolizumab; Drug: Carboplatin; Drug: 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.

Drug: Atezolizumab; Drug: RO6958688; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: 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.

Drug: Atezolizumab; Drug: Bevacizumab; Other: Radiation

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.

Drug: Atezolizumab; Drug: Evolocumab

Stage 1: Cohort 1: Atezolizumab + Tiragolumab

ACTIVE COMPARATOR

Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab; Drug: Tiragolumab

Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)

EXPERIMENTAL

Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab; Drug: Tiragolumab; Drug: XL092

Stage 1: Cohort 2: Atezolizumab + Camonsertib

EXPERIMENTAL

Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab; Drug: Camonsertib

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib

EXPERIMENTAL

Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Camonsertib

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab

EXPERIMENTAL

Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.

Stage 1: Cohort 1: Atezolizumab; Stage 1: Cohort 1: Atezolizumab + Cobimetinib; Stage 1: Cohort 1: Atezolizumab + RO6958688; Stage 1: Cohort 1: Atezolizumab + Tiragolumab; Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib); Stage 1: Cohort 2: Atezolizumab + Bevacizumab; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab; Stage 1: Cohort 2: Atezolizumab + CPI-444; Stage 1: Cohort 2: Atezolizumab + Camonsertib; Stage 1: Cohort 2: Atezolizumab + Cobimetinib; Stage 1: Cohort 2: Atezolizumab + Docetaxel; Stage 1: Cohort 2: Atezolizumab + Evolocumab; Stage 1: Cohort 2: Atezolizumab + Ipatasertib; Stage 1: Cohort 2: Atezolizumab + RO6958688; Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan; Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin; Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin; Stage 2: Cohort 2: Atezolizumab + Docetaxel; Stage 2: Cohort 2: Atezolizumab + Linagliptin; Stage 2: Cohort 2: Atezolizumab + RO6958688

Cobimetinib DRUG

Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.

Stage 1: Cohort 1: Atezolizumab + Cobimetinib; Stage 1: Cohort 2: Atezolizumab + Cobimetinib

RO6958688 DRUG

Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle.

Stage 1: Cohort 1: Atezolizumab + RO6958688; Stage 1: Cohort 2: Atezolizumab + RO6958688; Stage 2: Cohort 2: Atezolizumab + RO6958688

XL092 DRUG

XL092 is administered orally once a day on Day 1 to Day 21 of a 21 day cycle.

Also known as: Zanzalintinib

Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)

Docetaxel DRUG

Docetaxel is administered by IV on Day 1 of each 21 day cycle.

Stage 1: Cohort 2: Atezolizumab + Docetaxel; Stage 1: Cohort 2: Docetaxel; Stage 2: Cohort 2: Atezolizumab + Docetaxel

CPI-444 DRUG

CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle.

Stage 1: Cohort 2: Atezolizumab + CPI-444

Pemetrexed DRUG

Pemetrexed is administered by IV on Day 1 of a 21 day cycle.

Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin

Carboplatin DRUG

Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.

Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin; Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin

Gemcitabine DRUG

Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle.

Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin

Linagliptin DRUG

Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle.

Stage 2: Cohort 2: Atezolizumab + Linagliptin

Tocilizumab DRUG

Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.

Stage 1: Cohort 1: Atezolizumab + RO6958688; Stage 1: Cohort 2: Atezolizumab + RO6958688; Stage 2: Cohort 2: Atezolizumab + RO6958688

Ipatasertib DRUG

Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.

Stage 1: Cohort 2: Atezolizumab + Ipatasertib

Bevacizumab DRUG

Bevacizumab is administered by IV on Day 1 of each 21-day cycle.

Stage 1: Cohort 2: Atezolizumab + Bevacizumab; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy; Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab

Sacituzumab Govitecan DRUG

Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.

Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan

Radiation OTHER

Radiotherapy up to 21 days

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy

Evolocumab DRUG

Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each 28-day cycle.

Stage 1: Cohort 2: Atezolizumab + Evolocumab

Tiragolumab DRUG

Tiragolumab is administered on Day 1 of each 21 day cycle.

Stage 1: Cohort 1: Atezolizumab + Tiragolumab; Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib); Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab

Camonsertib DRUG

Camonsertib is administered orally on Days 1-3, Days 8-10 of a 21 day cycle.

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib; Stage 1: Cohort 2: Atezolizumab + Camonsertib

Eligibility Criteria

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

You may qualify if:

• 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
• 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
• No prior systemic therapy for metastatic NSCLC
• High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) or TCs \>= 50% or TC3
• \- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (29)

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, 89169, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Peter Mac Callum Cancer Center

East Melbourne, Victoria, 3002, Australia

Location

Centre Georges Francois Leclerc

Dijon, 21000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hopital de la Timone

Marseille, 13005, France

Location

Institut Régional du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut De Cancerologie De L'Ouest

Saint-Herblain, 44115, France

Location

Institut Universitaire du Cancer de Toulouse-Oncopole

Toulouse, 31100, France

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52620-00, Israel

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)

Songpa-gu, 05505, South Korea

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 280146, Spain

Location

Fundación Jimenez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, 28050, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Barts Cancer Institute

London, E1 2AT, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; cobimetinib; Docetaxel; ciforadenant; Pemetrexed; Carboplatin; Gemcitabine; Linagliptin; tocilizumab; ipatasertib; Bevacizumab; sacituzumab govitecan; Radiation; evolocumab; Tiragolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Quinazolines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Physical Phenomena

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 9, 2017
• Study Start: December 27, 2017
• Primary Completion: October 14, 2025
• Study Completion: November 25, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); KR (4); IL (3); FR (6); US (4); ES (7); GB (3)