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A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)

NCT04302025 · Genentech, Inc.
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Official title
NAUTIKA1: A Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-selected Patients With Resectable Stages IB-III Non-small Cell Lung Cancer
About this study
This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria.
Eligibility 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 participants will undergo clinical staging using computed tomography (CT) and positron emission tomography (PET) scanning, as well as brain imaging using magnetic resonance imaging (MRI). Invasive mediastinal staging by either mediastinoscopy or endo-bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (i.e., N2) but not mandated if the CT or PET scans showed no evidence of N2 disease * Molecular testing results from clinical laboratory improvement amendments (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 Food and Drug Administration (FDA)-approved test, KRAS G12C mutation * 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) deoxyribonucleic acid (DNA) test at screening * Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (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 participants 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 human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria: cluster of differentiation 4 (CD4)+ T-cell count of \<350 cells/microliters (cells/µL); 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
Study design
Enrollment target: 99 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2020-11-06
Estimated completion: 2030-05-30
Last updated: 2026-07-09
Interventions
Drug: AlectinibDrug: EntrectinibDrug: VemurafenibDrug: CobimetinibDrug: PralsetinibDrug: AtezolizumabDrug: SBRTProcedure: ResectionDrug: ChemotherapyDrug: Divarasib
Primary outcomes
  • Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) (After surgical resection (approximately study Week 8))
  • Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) (After surgical resection (approximately study Week 8))
  • KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) (After surgical resection (approximately study Week 8))
Sponsor
Genentech, Inc. · industry
Contacts & investigators
ContactReference Study ID Number: ML41591 https://forpatients.roche.com/ · contact · global-roche-genentech-trials@gene.com · 888-662-6728
ContactFastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry · contact
InvestigatorClinical Trials · study_director, Hoffmann-La Roche
All locations (38)
City of Hope Comprehensive Cancer CenterWithdrawn
Duarte, California, United States
City of Hope - Orange County Lennar Foundation Cancer CenterWithdrawn
Irvine, California, United States
USC Norris Cancer CenterWithdrawn
Los Angeles, California, United States
Cedars-Sinai Medical CenterWithdrawn
Los Angeles, California, United States
University of California Los Angeles - Jonsson Comprehensive Cancer CenterRecruiting
Los Angeles, California, United States
The Center for Cancer Prevention and Treatment at St.Joseph Hospital of OrangeRecruiting
Orange, California, United States
UC Davis Comprehensive Cancer CenterRecruiting
Sacramento, California, United States
UCSF Helen Diller Family CCCWithdrawn
San Francisco, California, United States
University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)Withdrawn
Aurora, Colorado, United States
Yale Cancer CenterRecruiting
New Haven, Connecticut, United States
MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)Recruiting
Washington D.C., District of Columbia, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Northwestern UniversityRecruiting
Chicago, Illinois, United States
Northwestern Medicine Cancer Center KishwaukeeRecruiting
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center DelnorRecruiting
Geneva, Illinois, United States
Northwestern Medicine Cancer Center WarrenvilleRecruiting
Warrenville, Illinois, United States
Boston Medical CenterWithdrawn
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment CenterWithdrawn
Farmington Hills, Michigan, United States
Mayo ClinicRecruiting
Rochester, Minnesota, United States
Ellis Fischel Cancer CenterRecruiting
Columbia, Missouri, United States
Siteman Cancer Center - Washington University Medical CampusRecruiting
St Louis, Missouri, United States
Dartmouth Hitchcock Medical CenterRecruiting
Lebanon, New Hampshire, United States
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.Recruiting
New York, New York, United States
Columbia University Medical CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
University Hospitals Cleveland Medical CenterWithdrawn
Cleveland, Ohio, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
AHN Cancer Institute ? Allegheny General HospitalCompleted
Pittsburgh, Pennsylvania, United States
Baptist Clinical Research InstituteRecruiting
Memphis, Tennessee, United States
Tennessee Oncology - NashvilleWithdrawn
Nashville, Tennessee, United States
Kelsey Seybold ClnicWithdrawn
Houston, Texas, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Baylor College of MedicineWithdrawn
Houston, Texas, United States
Lumi ResearchWithdrawn
Kingwood, Texas, United States
Virginia Cancer Specialists (Fairfax) - USORRecruiting
Fairfax, Virginia, United States
Seattle Cancer Care AllianceWithdrawn
Seattle, Washington, United States
A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) · TrialPath