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

Roche

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Ipatasertib; Drug: XL092; Drug: Linagliptin; Drug: Tocilizumab; Other: Radiation; Drug: Tiragolumab; Drug: Camonsertib; Drug: Bevacizumab; Drug: Sacituzumab Govitecan; Drug: Gemcitabine; Drug: Cobimetinib; Drug: Carboplatin; Drug: CPI-444; Drug: Atezolizumab; Drug: RO6958688; Drug: Pemetrexed; Drug: Docetaxel; Drug: Evolocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03337698

2017-001267-21 (EudraCT Number)

BO39610

Details and patient eligibility

About

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).

Enrollment: 675 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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
• 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) or TCs >= 50% or TC3

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

675 participants in 23 patient groups

Stage 1: Cohort 1: Atezolizumab

Active Comparator group

Description:

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.

Treatment:

Drug: Atezolizumab

Stage 1: Cohort 1: Atezolizumab + Cobimetinib

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Cobimetinib

Stage 1: Cohort 1: Atezolizumab + RO6958688

Experimental group

Description:

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.

Treatment:

Drug: RO6958688

Drug: Atezolizumab

Drug: Tocilizumab

Stage 1: Cohort 2: Docetaxel

Active Comparator group

Description:

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.

Treatment:

Drug: Docetaxel

Stage 1: Cohort 2: Atezolizumab + Cobimetinib

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Cobimetinib

Stage 1: Cohort 2: Atezolizumab + CPI-444

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: CPI-444

Stage 1: Cohort 2: Atezolizumab + RO6958688

Experimental group

Description:

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.

Treatment:

Drug: RO6958688

Drug: Atezolizumab

Drug: Tocilizumab

Stage 1: Cohort 2: Atezolizumab + Ipatasertib

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Ipatasertib

Stage 1: Cohort 2: Atezolizumab + Docetaxel

Experimental group

Description:

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.

Treatment:

Drug: Docetaxel

Drug: Atezolizumab

Stage 1: Cohort 2: Atezolizumab + Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Bevacizumab

Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin

Experimental group

Description:

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

Treatment:

Drug: Pemetrexed

Drug: Atezolizumab

Drug: Carboplatin

Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Carboplatin

Drug: Gemcitabine

Stage 2: Cohort 2: Atezolizumab + RO6958688

Experimental group

Description:

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

Treatment:

Drug: RO6958688

Drug: Atezolizumab

Drug: Tocilizumab

Stage 2: Cohort 2: Atezolizumab + Docetaxel

Experimental group

Description:

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.

Treatment:

Drug: Docetaxel

Drug: Atezolizumab

Stage 2: Cohort 2: Atezolizumab + Linagliptin

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Linagliptin

Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Sacituzumab Govitecan

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Bevacizumab

Other: Radiation

Stage 1: Cohort 2: Atezolizumab + Evolocumab

Experimental group

Description:

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

Treatment:

Drug: Evolocumab

Drug: Atezolizumab

Stage 1: Cohort 1: Atezolizumab + Tiragolumab

Active Comparator group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

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

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Drug: XL092

Stage 1: Cohort 2: Atezolizumab + Camonsertib

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Camonsertib

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Camonsertib

Drug: Bevacizumab

Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Bevacizumab

Drug: Tiragolumab