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

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.

Conditions

• Non-Small Cell Lung Cancer

Interventions

DRUG

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.

DRUG

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).

DRUG

Pemetrexed

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

DRUG

Cisplatin

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

DRUG

Carboplatin

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

DRUG

Gemcitabine

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

DRUG

Entrectinib

Participants will receive entrectinib 600 mg orally QD.

DRUG

Cobimetinib

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

DRUG

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.

DRUG

Bevacizumab

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

DRUG

Divarasib

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

DRUG

Docetaxel

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

Sponsors & Collaborators

• Hoffmann-La Roche

  lead INDUSTRY

Principal Investigators

• Clinical Trials · Hoffmann-La Roche

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-09-22

Primary Completion

2026-10-31

Completion

2026-10-31

FDA Drug

Yes

Countries

• United States
• Argentina
• Australia
• Belgium
• Brazil
• Canada
• Chile
• China
• France
• Germany
• Hong Kong
• Israel
• Italy
• Japan
• Mexico
• New Zealand
• Panama
• Peru
• Poland
• Russia
• Serbia
• Singapore
• South Korea
• Spain
• Taiwan
• Thailand
• Turkey (Türkiye)

Study Locations