Purpose

This trial will evaluate the efficacy and safety of targeted therapies in participants with resectable Stage IA2, IB, IIIA, or selected IIIB 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

Neoadjuvant Therapy: - Pathologically documented NSCLC - Molecular testing results from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories and showing at least one of the following abnormalities: ALK gene rearrangement; ROS1 gene rearrangement; NTRK1/2/3 gene rearrangement; BRAF V600 mutation - Molecular testing results used for patient eligibility should be obtained from the most recent tumor biopsy. Alternatively, and for patients with ALK, ROS1, and NTRK1/2/3 molecular alterations, molecular testing results used to determine patient eligibility could have been obtained from a recent blood sample (up to 2 months prior to enrollment) described in the study design - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - NSCLC must have a solid or subsolid appearance on computed tomography (CT) scan and cannot have a purely ground glass opacity appearance. For sub-solid lesions, the tumor size (i.e., clinical T stage) should be measured based on the solid component only, exclusive of the ground glass opacity component - 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 patient 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 - Adequate hematologic and end-organ function - Male patients must be willing to use acceptable methods of contraception. Treatment-specific contraceptive requirements will be in the specific protocol appendix for each study drug - Female patients of childbearing potential must agree to use acceptable methods of contraception. For treatment-specific contraceptive requirements, please see the specific appendix for each study drug Adjuvant Therapy: - Patients whose tumors have pathologic response or lack of 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 - Patients 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 - Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of patients with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, non-muscle invasive bladder cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per SOC management (e.g., Rai Stage 0 chronic lymphocytic leukemia, prostate cancer with Gleason score </= 6, and prostate-specific antigen (</= 10 ng/mL, etc.) - Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1 (or within 5 half-lives of the investigational product, whichever is longer) - Known HIV positivity or AIDS-related illness - 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
Patients will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with alectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
  • 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
  • Radiation: Radiotherapy
    Participants will receive radiotherapy as deemed appropriate by the treating physician
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
ROS 1 Cohort
Patients will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
  • Drug: Entrectinib
    Participants will receive oral entrectinib daily
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Radiation: Radiotherapy
    Participants will receive radiotherapy as deemed appropriate by the treating physician
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
NTRK Cohort
Patients will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
  • Drug: Entrectinib
    Participants will receive oral entrectinib daily
  • Procedure: Resection
    Participants will receive surgical resection of the primary tumor along with selected lymph nodes
  • Radiation: Radiotherapy
    Participants will receive radiotherapy as deemed appropriate by the treating physician
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
Experimental
BRAF Cohort
Patients will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients 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. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
  • 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
  • Radiation: Radiotherapy
    Participants will receive radiotherapy as deemed appropriate by the treating physician
  • Drug: Chemotherapy
    Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician

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.