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A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04302025
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : July 12, 2022
Sponsor:
Collaborator:
Blueprint Medicines Corporation
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
This trial will evaluate the efficacy and safety of various therapies in patients with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated non-small cell lung cancer (NSCLC) tumors that meet protocol-specified biomarker criteria

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 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 Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer
Actual Study Start Date : November 6, 2020
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : February 28, 2029

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.
Drug: Pralsetinib
Participants will receive oral pralsetinib 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: PD-L1 Cohort
Participants with positive PD-L1 in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, patients will also receive low-dose SBRT (8Gy X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per NCCN guidelines
Drug: Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion

Drug: SBRT
Patients will receive SBRT given concurrently starting with the first dose of atezolizumab

Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes




Primary Outcome Measures :
  1. Tyrosine kinase inhibitor (TKI): 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

  2. Checkpoint inhibitor (CPI) cohort: Pathological complete response (pCR) [ Time Frame: After surgical resection (approximately study Week 8) ]
    Scored by local pathologists; defined as lack of any viable tumor cells on review of hematoxylin and eosin (H&E) slides after complete evaluation of a resected lung cancer specimen including all sampled regional lymph nodes


Secondary Outcome Measures :
  1. Proportion of Participants with MPR [ Time Frame: After surgical resection (approximately study Week 8) ]
    Defined as ≤10% residual viable tumor cells) based on surgical resection as defined by Hellmann et al. (2014) and Travis et al. (2020) TKI cohorts: MPR will be scored by a central pathology committee consensus read CPI cohort: MPR will be scored by local pathologists and central pathology committee consensus read

  2. Proportion of Participants with pCR [ Time Frame: After surgical resection (approximately study Week 8) ]

    defined as lack of any viable tumor cells on review of H&E slides after complete evaluation of a resected lung cancer specimen, including all sampled regional lymph nodes

    • TKI cohorts: pCR will be scored by local pathologists and a central pathology committee consensus read
    • CPI cohort: pCR will be scored by a central pathology committee consensus read

  3. Pathological Regression Based on Weighted % Viable Tumor Cell Assessment [ Time Frame: After surgical resection (approximately study Week 8) ]
  4. Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1 [ Time Frame: After neoadjuvant treatment (after approximately study Week 8) ]
  5. 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

  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 8 years ]
  10. Nodal downstaging, defined as percentage of patients with reduced stages in mediastinal nodes at surgery [ Time Frame: After surgical resection (approximately study Week 8) ]
  11. Circulating tumor DNA 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 IB, 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
  • T4 primary NSCLC will be allowed only on the basis of size
  • All patients will undergo clinical staging using CT and PET scanning, as well as brain imaging using MRI. Invasive mediastinal staging by either mediastinoscopy or endo- bronchial ultrasonography is highly encouraged for patients with radiographically suspected mediastinal nodal disease (ie, N2) but not mandated if the CT or PET scans showed no evidence of N2 disease.
  • 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, PD-L1 expression in ≥ 1% tumor cells as determined by FDA-approved test
  • 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 26 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: July 12, 2022
Last Verified: July 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
Atezolizumab
Vemurafenib
Pralsetinib
Entrectinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action