Clinical Trials /

A Study of Alectinib, Entrectinib, Vemurafenib Plus Cobimetinib, or Pralsetinib in Patients With Resectable Stages II-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, BRAF V600, or RET Molecular Alterations

NCT04302025

Description:

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.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Alectinib, Entrectinib, Vemurafenib Plus Cobimetinib, or Pralsetinib in Patients With Resectable Stages II-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, BRAF V600, or RET Molecular Alterations
  • Official Title: NAUTIKA1: Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Alectinib, Entrectinib, Vemurafenib Plus Cobimetinib, or Pralsetinib in Patients With Resectable Stages II-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, BRAF V600, or RET 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
PralsetinibRET Cohort

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.

Trial Arms

NameTypeDescriptionInterventions
ALK CohortExperimentalParticipants 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.
  • Alectinib
  • Chemotherapy
ROS 1 CohortExperimentalParticipants 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.
  • Entrectinib
  • Chemotherapy
NTRK CohortExperimentalParticipants 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.
  • Entrectinib
  • Chemotherapy
BRAF CohortExperimentalParticipants 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.
  • Vemurafenib
  • Cobimetinib
  • Chemotherapy
RET CohortExperimentalParticipants 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.
  • Chemotherapy
  • Pralsetinib

Eligibility Criteria

        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
      
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 as scored by local pathologists

Secondary Outcome Measures

Measure:Proportion of Participants with MPR as Scored by a Central Pathology Committee
Time Frame:After surgical resection (approximately study Week 8)
Safety Issue:
Description:MPR is defined as </=10% residual viable tumor cells
Measure:Pathological Regression Based on Weighted % 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 Local and Central Pathology Laboratories
Time Frame:At the time of surgical resection (approximately study Week 8)
Safety Issue:
Description:Defined as the absence of any viable tumor in main tumor bed at the time of surgical resection, as assessed by local and central pathology laboratories
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:
Measure:ctDNA Clearance Rate
Time Frame:Prior to surgery (before study Week 8)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

May 26, 2021