A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III 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 oral alectinib twice per day (BID).
• Entrectinib — DRUG
  Participants will receive oral entrectinib daily.
• Vemurafenib — DRUG
  Participants will receive oral vemurafenib BID.
• Cobimetinib — DRUG
  Participants will receive oral cobimetinib daily.
• Pralsetinib — DRUG
  Participants will receive oral pralsetinib daily.
• Atezolizumab — DRUG
  Atezolizumab will be administered by intravenous (IV) infusion.
• SBRT — DRUG
  Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.
• Resection — PROCEDURE
  Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.
• Chemotherapy — DRUG
  Participants will receive SOC chemotherapy as determined by the treating physician.
• Divarasib — DRUG
  Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy.

Study Details

This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria.

Key Dates

Start date

Nov 6, 2020

Status verified

Jun 2026

Primary completion

Nov 30, 2026

Completion

May 30, 2030

Study Design

Enrollment

99 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: ALK Cohort (Enrolment Closed)
  Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care (SOC). All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib. Enrolment Closed.
• Experimental: ROS 1 Cohort (Enrolment Closed)
  Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed.
• Experimental: NTRK Cohort (Enrolment Closed)
  Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed.
• Experimental: BRAF Cohort (No Participants Enrolled, Cohort Closed)
  Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib. Cohort closed.
• Experimental: RET Cohort (Cohort closed)
  Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib. Cohort closed.
• Experimental: PD-L1 Cohort (Enrolment Closed)
  Participants with positive programmed death-ligand 1 (PD-L1) in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, participants will also receive low-dose stereotactic body radiation therapy (SBRT) (8 gray \[Gy\] X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per National Comprehensive Cancer Network (NCCN) guidelines. Enrolment Closed.
• Experimental: KRAS G12C Cohort
  Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per SOC. PD-L1 negative participants whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib alone for up to 3 years or 1-4 cycles of SOC chemotherapy followed by divarasib for 3 years as adjuvant therapy. For participants who test positive PD-L1, they will have the option to receive 1-4 cycles of SOC chemotherapy followed by atezolizumab for up to 16 cycles or SOC alone.

Primary Outcome Measure

Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) [ Time Frame: After surgical resection (approximately study Week 8) ]

Central Contacts

• Reference Study ID Number: ML41591 https://forpatients.roche.com/
  888-662-6728
  [email protected]
• Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Locations (38)

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