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 : May 1, 2024
|
Sponsor:
Genentech, Inc.
Information provided by (Responsible Party):
Genentech, Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 (Enrollment closed) Drug: Cobimetinib (Enrollment closed) Drug: Pralsetinib (Enrollment closed) Drug: Atezolizumab Drug: SBRT Procedure: Resection Drug: Chemotherapy Drug: Divarasib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 125 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 : | December 30, 2025 |
| Estimated Study Completion Date : | March 6, 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
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 (Enrollment closed, no participants enrolled)
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. Enrollment closed. |
Drug: Vemurafenib (Enrollment closed)
Participants will receive oral vemurafenib BID Drug: Cobimetinib (Enrollment closed) 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 (Enrollment closed)
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. Enrollment closed. |
Drug: Pralsetinib (Enrollment closed)
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 |
|
Experimental: KRAS G12C Cohort
Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per standard of care. PD-L1 negative patients whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib for up to 2 years as adjuvant therapy. For patients who test positive PD-L1, they will have the option to receive Atezolizumab for up to 16 cycles.
|
Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes Drug: Divarasib Participants in the KRAS G12C cohort will receive divarasib for approximately 8 weeks until the day before surgery. |
Primary Outcome Measures :
- Tyrosine kinase inhibitor (TKI) cohort: 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
- 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
- KRAS cohort: Percentage of participants with 3-5 grade Adverse Events [ Time Frame: After surgical resection (approximately study Week 8) ]
- KRAS cohort: Percentage of participants without delays of surgery due to treatment-related adverse events as reported by the investigator [ Time Frame: After surgical resection (approximately study Week 8) ]
Secondary Outcome Measures :
- 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 KRAS G12C cohort: MPR will be scored by local pathologists and central pathology committee consensus read
- 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 KRAS G12C cohort: pCR will be scored by local pathologists and a central pathology committee consensus read
- Pathological Regression Based on Weighted % Viable Tumor Cell Assessment [ Time Frame: After surgical resection (approximately study Week 8) ]
- Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1 [ Time Frame: After neoadjuvant treatment (after approximately study Week 8) ]
- 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
- 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) ]
- 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) ]
- 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) ]
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 8 years ]
- Nodal downstaging, defined as percentage of patients with reduced stages in mediastinal nodes at surgery [ Time Frame: After surgical resection (approximately study Week 8) ]
- Circulating tumor DNA ctDNA Clearance Rate [ Time Frame: Prior to surgery (before study Week 8) ]
- KRAS G12C cohort: Plasma concentration of divarasib at specified timepoints [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (Cycle= 28 days) ]
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.
| 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:
- Newly diagnosed early-stage NSCLC stages IB, IIA, IIB, IIIA, or selected IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) NSCLC staging system.
- T4 primary NSCLC will be allowed only on the basis of size. Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted.
- All patients will undergo clinical staging using CT and PET scanning, as well as brain imaging using MRI. Invasive mediastinal staging by either mediastinoscopyor 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 (enrollment closed); RET fusion (enrollment closed), PD-L1, KRAS G12C expression in ≥ 1% tumor cells as determined by FDA-approved test.
- Measurable disease, as defined by RECIST v1.1
- NSCLC must have a solid or subsolid appearance on CT scan and cannot have a purely ground glass opacity appearance. For subsolid 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 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
- Adequate hematologic and end-organ function
- Negative hepatitis B surface antigen (HBsAg) test at screening for cohort
- Negative total hepatitits B core antibody (HBcAb) test at screening for cohort, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- 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 (TKI Cohorts and KRAS G12C cohort [if continuing on Divarasib]):
- 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
- 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
- Treatment with an investigational agent for any condition within 4 weeks 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
| Contact: Reference Study ID Number: ML41591 https://forpatients.roche.com/ | 888-662-6728 | global-roche-genentech-trials@gene.com |
Locations
Show 35 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Genentech, Inc. |
| ClinicalTrials.gov Identifier: | NCT04302025 |
| Other Study ID Numbers: |
ML41591 |
| First Posted: | March 10, 2020 Key Record Dates |
| Last Update Posted: | May 1, 2024 |
| Last Verified: | April 2024 |
| 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). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
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 Alectinib Entrectinib Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Tyrosine Kinase Inhibitors |