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A Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Participants With Stages I-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, or BRAF v600E Molecular Alterations

NCT04302025

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Participants With Stages I-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, or BRAF v600E Molecular Alterations
  • Official Title: Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Patients With Stages I-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, or BRAF v600E Molecular Alterations

Clinical Trial IDs

  • ORG STUDY ID: ML41591
  • NCT ID: NCT04302025

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
AlectinibALK Cohort
EntrectinibNTRK Cohort
VemurafenibBRAF Cohort
CobimetinibBRAF Cohort
ChemotherapyALK Cohort

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.

Trial Arms

NameTypeDescriptionInterventions
ALK CohortExperimentalPatients 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.
  • Alectinib
  • Chemotherapy
ROS 1 CohortExperimentalPatients 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.
  • Entrectinib
  • Chemotherapy
NTRK CohortExperimentalPatients 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.
  • Entrectinib
  • Chemotherapy
BRAF CohortExperimentalPatients 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.
  • Vemurafenib
  • Cobimetinib
  • Chemotherapy

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of Participants with Major Pathologic Response (MPR)
Time Frame:After surgical resection (approximately study Week 8)
Safety Issue:
Description:MPR is defined as </=10% residual viable tumor cells

Secondary Outcome Measures

Measure:Pathological Regression Based on % Viable Tumor Cell Assessment
Time Frame:After surgical resection (approximately study Week 8)
Safety Issue:
Description:
Measure:Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1
Time Frame:After neoadjuvant treatment (after approximately study Week 8)
Safety Issue:
Description:
Measure:Pathological Complete Response (pCR) as Assessed by Investigator Site Pathology Laboratory
Time Frame:At the time of surgical resection (approximately study Week 8)
Safety Issue:
Description:pCR is defined as the absence of residual invasive in situ cancer and all sampled regional lymph nodes
Measure:Disease-Free Survival (DFS)
Time Frame:From the first date of no disease to local or distant recurrence or death from any cause, whichever occurs first, through the end of the study (up to 8 years)
Safety Issue:
Description:
Measure:Event-Free Survival (EFS)
Time Frame:From first dose of study treatment to first documented disease progression per RECIST v1.1, or local or distant disease recurrence as determined by investigator, or death from any cause, whichever occurs first, through the end of study (up to 8 years)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From the first dose of study medication to death from any cause, through the end of the study (up to 8 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Up to 8 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

May 29, 2020