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

Conditions

• Non-Small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Alectinib — DRUG
  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 — DRUG
  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 — DRUG
  Participants will receive pemetrexed 500 mg/m\^2 IV infusion on Day 1 Q21D.
• Cisplatin — DRUG
  Participants will receive cisplatin 75 mg/m\^2 IV on Day 1 Q21D.
• Carboplatin — DRUG
  Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.
• Gemcitabine — DRUG
  Participants will receive gemcitabine 1000 or 1250 mg/m\^2 on Days 1 and 8 of every cycle (1 Cycle=21 days).
• Entrectinib — DRUG
  Participants will receive entrectinib 600 mg orally QD.
• Cobimetinib — DRUG
  Participants will receive 60 mg PO QD on Days 1-21 of the initial run-in and triple-combination periods.
• Vemurafenib — DRUG
  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 — DRUG
  Participants will receive 15 mg/kg of IV bevacizumab on Day 1 of each 21-day cycle during the induction and maintenance periods.
• Divarasib — DRUG
  Participants will receive divarasib PO QD until disease progression or unacceptable toxicity.
• Docetaxel — DRUG
  Participants will receive IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity

Study Details

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.

Key Dates

Start date

Sep 22, 2017

Status verified

Jun 2026

Primary completion

Oct 31, 2026

Completion

Oct 31, 2026

Study Design

Enrollment

1,000 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A: Alectinib 600 Milligrams (mg)
  This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort A is complete.
• Experimental: Cohort B: Dose Finding Phase (DFP) Alectinib
  This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose. Enrollment to Cohort B is complete.
• Experimental: Cohort B: Dose Expansion Phase (DEP) Alectinib
  This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort B is complete.
• Experimental: Cohort C: Atezolizumab 1200 mg
  This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort C is complete.
• Active Comparator: Cohort C: Pemetrexed, Cisplatin or Carboplatin
  This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete.
• Active Comparator: Cohort C: Gemcitabine, Cisplatin or Carboplatin
  This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete.
• Experimental: Cohort D: Entrectinib 600 Milligrams (mg)
  This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort D is complete.
• Experimental: Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib
  This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete.
• Experimental: Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed
  This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete.
• Experimental: Cohort G: Divarasib or Docetaxel
  Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel.
• No Intervention: Cohort Z: Natural History Cohort
  Participants with genomic profiles of interest that are not enrolled in the other cohorts will enter into natural history follow-up.

Primary Outcome Measure

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 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]

Locations (12)

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