Purpose

This trial will evaluate the efficacy and safety of targeted therapies in participants with resectable Stage IIA, IIB, IIIA, and select IIIB (T3N2) resectable and untreated non-small cell lung cancer (NSCLC) tumors with selected molecular alterations.

Condition

Eligibility

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

Inclusion Criteria

for Neoadjuvant Therapy: - Pathologically documented NSCLC: Stage IIA, IIB, IIIA, or selected IIIB, including T3N2, or T4 (by size criteria, not by mediastinal invasion) NSCLC (based on the 8th edition of the American Joint Committee on Cancer [AJCC] Non-Small Cell Lung Cancer Staging system - Molecular testing results from CLIA-certified laboratories and showing at least one of the following abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation; RET fusion - Measurable disease, as defined by RECIST v1.1 - Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the participant is medically operable - Adequate pulmonary function to be eligible for surgical resection with curative intent - Adequate cardiac function to be eligible for surgical resection with curative intent - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Male participants must be willing to use acceptable methods of contraception - Female participants of childbearing potential must agree to use acceptable methods of contraception Inclusion Criteria for Adjuvant Therapy - Participants whose tumors lack radiographic progression - ECOG Performance Status of 0 or 1 - Adequate hematologic and end-organ function

Exclusion Criteria

  • NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease - Any prior therapy for lung cancer, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years - Participants with prior lung cancer that have been in remission for <2 years with the exception of minimally invasive adenocarcinoma or incidental typical carcinoid tumors - Major surgical procedure within 28 days prior to Cycle 1, Day 1 - Participants known to be positive for HIV are excluded if they meet any of the following criteria: CD4+ T-cell count of <350 cells/microliters; detectable HIV viral load; history of an opportunistic infection within the past 12 months; on stable antiretroviral therapy for <4 weeks - Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety - Pregnant or lactating, or intending to become pregnant during the study

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ALK Cohort
Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
  • Drug: Alectinib
    Participants will receive oral alectinib twice per day (BID)
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
ROS 1 Cohort
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
  • Drug: Entrectinib
    Participants will receive oral entrectinib daily
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
NTRK Cohort
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
  • Drug: Entrectinib
    Participants will receive oral entrectinib daily
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
BRAF Cohort
Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
  • Drug: Vemurafenib
    Participants will receive oral vemurafenib BID
  • Drug: Cobimetinib
    Participants will receive oral cobimetinib daily
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
RET Cohort
Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
  • Drug: Pralsetinib
    Participants will receive oral pralsetinib daily

Recruiting Locations

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
Washington, District of Columbia 20007

More Details

Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: ML41591 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.