A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)

Condition(s) studied

Investigational drug(s) / intervention(s)

Alectinib: Participants will receive 600 mg BID (Cohort A); 900, 1200, or 750 mg BID (Cohort B) or RP2D BID; orally until disease progression, unacceptable toxicity, withdrawal of consent or death.

Atezolizumab: Participants will receive atezolizumab 1200 mg IV infusion Q21D (Cohorts C and F) or 1680 mg IV infusion Q4W starting on Day 29 (Cohort E).

Pemetrexed: Participants will receive pemetrexed 500 mg/m\^2 IV infusion on Day 1 Q21D.

Cisplatin: Participants will receive cisplatin 75 mg/m\^2 IV on Day 1 Q21D.

Carboplatin: Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.

Gemcitabine: Participants will receive gemcitabine 1000 or 1250 mg/m\^2 on Days 1 and 8 of every cycle (1 Cycle=21 days).

Entrectinib: Participants will receive entrectinib 600 mg orally QD.

Cobimetinib: Participants will receive 60 mg PO QD on Days 1-21 of the initial run-in and triple-combination periods.

Vemurafenib: Participants will receive 960 mg PO BID on Days 1-21 of the initial run-in period, and 720 mg PO BID on Days 22-28 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period.

Bevacizumab: Participants will receive 15 mg/kg of IV bevacizumab on Day 1 of each 21-day cycle during the induction and maintenance periods.

Divarasib: Participants will receive divarasib PO QD until disease progression or unacceptable toxicity.

Docetaxel: Participants will receive IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity

Study summary

This is a phase 2/3, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (TMB) assay as identified by a blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assay.

Eligibility

Primary outcome measure(s)

• Cohort A: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 — Baseline up to disease progression or death (up to approximately 6 years)
• Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1 — Baseline up to disease progression or death (up to approximately 6 years)
• Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1 — Baseline up to disease progression or death (up to approximately 6 years)
• Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1 — Baseline up to disease progression or death (up to approximately 6 years)
• Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1 — Month 12
• Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1 — Baseline up to disease progression or death (up to approximately 6 years)
• Cohort G: Incidence of Adverse Events (AEs) — Baseline to last dose of study treatment + 30 days or until initiation of new anticancer therapy, whichever occurs first (up to approximately 6 years)

Trial sites (161)

+ 121 more sites — see the full list on the official registry below.

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