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

Roche

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Docetaxel; Drug: Entrectinib; Drug: Pemetrexed; Drug: Atezolizumab; Drug: Cisplatin; Drug: Cobimetinib; Drug: Gemcitabine; Drug: Alectinib; Drug: Divarasib; Drug: Bevacizumab; Drug: Carboplatin; Drug: Vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03178552

2017-000076-28 (EudraCT Number)

BO29554

Details and patient eligibility

About

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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Measurable disease
• Adequate recovery from most recent systemic or local treatment for cancer
• Adequate organ function
• Life expectancy greater than or equal to (>/=) 12 weeks
• For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception

Exclusion criteria

• Inability to swallow oral medication
• Women who are pregnant or lactating
• Symptomatic, untreated CNS metastases
• History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
• Known active or uncontrolled human immunodeficiency virus (HIV) infection
• Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
• Inability to comply with other requirements of the protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,000 participants in 11 patient groups

Cohort A: Alectinib 600 Milligrams (mg)

Experimental group

Description:

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.

Treatment:

Drug: Alectinib

Cohort B: Dose Finding Phase (DFP) Alectinib

Experimental group

Description:

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.

Treatment:

Drug: Alectinib

Cohort B: Dose Expansion Phase (DEP) Alectinib

Experimental group

Description:

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.

Treatment:

Drug: Alectinib

Cohort C: Atezolizumab 1200 mg

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Cohort C: Pemetrexed, Cisplatin or Carboplatin

Active Comparator group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin

Cohort C: Gemcitabine, Cisplatin or Carboplatin

Active Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Cisplatin

Drug: Carboplatin

Cohort D: Entrectinib 600 Milligrams (mg)

Experimental group

Description:

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.

Treatment:

Drug: Entrectinib

Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib

Experimental group

Description:

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.

Treatment:

Drug: Vemurafenib

Drug: Cobimetinib

Drug: Atezolizumab

Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Atezolizumab

Drug: Carboplatin

Drug: Bevacizumab

Cohort G: Divarasib or Docetaxel

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: Docetaxel

Cohort Z: Natural History Cohort

No Intervention group

Description:

Participants with genomic profiles of interest that are not enrolled in the other cohorts will enter into natural history follow-up.