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

Purpose

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 two blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assays.

Condition

  • Non-Small Cell Lung Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 human immunodeficiency virus (HIV) positivity or autoimmune deficiency syndrome (AIDS)-related illness - 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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • 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.
    Other names:
    • RO5424802
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.
  • 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.
    Other names:
    • RO5424802
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.
  • 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.
    Other names:
    • RO5424802
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.
  • 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).
    Other names:
    • RO5541267
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.
  • 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.
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.
  • 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).
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.
  • Drug: Entrectinib
    Participants will receive entrectinib 600 mg orally QD.
    Other names:
    • RO7102122
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.
  • 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).
    Other names:
    • RO5541267
  • Drug: Cobimetinib
    Participants will receive 60 mg PO QD on Days 1-21 of the initial run-in and triple-combination periods.
    Other names:
    • RO5514041
  • 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.
    Other names:
    • RO5185426
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.
  • 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).
    Other names:
    • RO5541267
  • Drug: Pemetrexed
    Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D.
  • Drug: Carboplatin
    Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.
  • 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.
    Other names:
    • RO4876646
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
  • Drug: GDC-6036
    Participants will receive GDC-6036 PO QD until disease progression or unacceptable toxicity.
    Other names:
    • RO7435846
  • Drug: Docetaxel
    Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10461

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: BO29554 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com