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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

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ClinicalTrials.gov Identifier: NCT04302025
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : January 11, 2022
Sponsor:
Collaborator:
Blueprint Medicines Corporation
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
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 or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Alectinib Drug: Entrectinib Drug: Vemurafenib Drug: Cobimetinib Procedure: Resection Drug: Chemotherapy Drug: Pralsetinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2020
Estimated Primary Completion Date : August 15, 2028
Estimated Study Completion Date : August 15, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Proportion of Participants with Major Pathologic Response (MPR) [ Time Frame: After surgical resection (approximately study Week 8) ]
    MPR is defined as </=10% residual viable tumor cells as scored by local pathologists


Secondary Outcome Measures :
  1. Proportion of Participants with MPR as Scored by a Central Pathology Committee [ Time Frame: After surgical resection (approximately study Week 8) ]
    MPR is defined as </=10% residual viable tumor cells

  2. Pathological Regression Based on Weighted % Viable Tumor Cell Assessment [ Time Frame: After surgical resection (approximately study Week 8) ]
  3. Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1 [ Time Frame: After neoadjuvant treatment (after approximately study Week 8) ]
  4. Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories [ Time Frame: At the time of surgical resection (approximately study Week 8) ]
    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

  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 8 years ]
  9. ctDNA Clearance Rate [ Time Frame: Prior to surgery (before study Week 8) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04302025


Contacts
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Contact: Reference Study ID Number: ML41591 https://forpatients.roche.com/ 888-662-6728 global-roche-genentech-trials@gene.com

Locations
Show Show 24 study locations
Sponsors and Collaborators
Genentech, Inc.
Blueprint Medicines Corporation
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT04302025    
Other Study ID Numbers: ML41591
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: January 11, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Vemurafenib
Pralsetinib
Entrectinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action