Immunotherapy Combinations for Non-Small Cell Lung Cancer

(Morpheus Lung Trial)

Recruiting in Palo Alto (17 mi)

+43 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Hoffmann-La Roche

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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).

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with metastatic non-small cell lung cancer. Cohort 1 includes those who haven't had systemic therapy and have high PD-L1 in tumors. Cohort 2 has patients whose disease progressed after platinum-based and PD-L1/PD-1 inhibitor treatments. Participants must be able to perform daily activities with minimal assistance, have a life expectancy of at least 3 months, measurable disease, proper organ function, and agree to use contraception.

Inclusion Criteria

My blood and organs are functioning well.

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

My lung cancer is confirmed to be non-small cell type and has spread.

Exclusion Criteria

I have a history of certain lung conditions or signs of lung inflammation on a chest scan.

I frequently need procedures to remove excess fluid from my body.

I have brain metastases that are untreated or getting worse.

Treatment Details

Interventions

• Atezolizumab (Immunotherapy Combination)
• Carboplatin (Chemotherapy)
• Pemetrexed (Chemotherapy)
• Radiation (Other)

Trial Overview The study tests various immunotherapy combinations on two groups: one untreated for metastatic NSCLC (high tumor PD-L1 expression), the other previously treated but progressed. It assesses effectiveness, safety, and drug behavior in the body over two stages—initial treatment followed by an alternative if needed due to progression or side effects.

Participant Groups

Group I: Stage 2: Cohort 2: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group II: Stage 2: Cohort 2: Atezolizumab + Linagliptin Experimental Treatment 2 Interventions

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

Group III: Stage 2: Cohort 2: Atezolizumab + Docetaxel Experimental Treatment 2 Interventions

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.

Group IV: Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin Experimental Treatment 3 Interventions

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

Group V: Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin Experimental Treatment 3 Interventions

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

Group VI: Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan Experimental Treatment 2 Interventions

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

Group VII: Stage 1: Cohort 2: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

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.

Group VIII: Stage 1: Cohort 2: Atezolizumab + Ipatasertib Experimental Treatment 2 Interventions

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.

Group IX: Stage 1: Cohort 2: Atezolizumab + Evolocumab Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.

Group X: Stage 1: Cohort 2: Atezolizumab + Docetaxel Experimental Treatment 2 Interventions

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.

Group XI: Stage 1: Cohort 2: Atezolizumab + Cobimetinib Experimental Treatment 2 Interventions

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.

Group XII: Stage 1: Cohort 2: Atezolizumab + Camonsertib Experimental Treatment 2 Interventions

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

Group XIII: Stage 1: Cohort 2: Atezolizumab + CPI-444 Experimental Treatment 2 Interventions

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.

Group XIV: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab Experimental Treatment 3 Interventions

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

Group XV: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy Experimental Treatment 3 Interventions

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

Group XVI: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib Experimental Treatment 3 Interventions

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

Group XVII: Stage 1: Cohort 2: Atezolizumab + Bevacizumab Experimental Treatment 2 Interventions

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.

Group XVIII: Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib) Experimental Treatment 3 Interventions

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

Group XIX: Stage 1: Cohort 1: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

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.

Group XX: Stage 1: Cohort 1: Atezolizumab + Cobimetinib Experimental Treatment 2 Interventions

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.

Group XXI: Stage 1: Cohort 2: Docetaxel Active Control 1 Intervention

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.

Group XXII: Stage 1: Cohort 1: Atezolizumab + Tiragolumab Active Control 2 Interventions

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

Group XXIII: Stage 1: Cohort 1: Atezolizumab Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University