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
Summary
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.
Arms & interventions
- DrugAlectinib
Participants will receive oral alectinib twice per day (BID).
- DrugEntrectinib
Participants will receive oral entrectinib daily.
- DrugVemurafenib
Participants will receive oral vemurafenib BID.
- DrugCobimetinib
Participants will receive oral cobimetinib daily.
- DrugPralsetinib
Participants will receive oral pralsetinib daily.
- DrugAtezolizumab
Atezolizumab will be administered by intravenous (IV) infusion.
- DrugSBRT
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.
- ProcedureResection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.
- DrugChemotherapy
Participants will receive SOC chemotherapy as determined by the treating physician.
- DrugDivarasib
Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy.
Outcome measures
Primary
Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR)
MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists.
Time frame: After surgical resection (approximately study Week 8)
Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR)
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.
Time frame: After surgical resection (approximately study Week 8)
KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Time frame: After surgical resection (approximately study Week 8)
KRAS G12C Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related AEs as Reported by the Investigator
Time frame: After surgical resection (approximately study Week 8)
Secondary
Proportion of Participants With MPR
Time frame: After surgical resection (approximately study Week 8)
Proportion of Participants With pCR
Time frame: After surgical resection (approximately study Week 8)
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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: After neoadjuvant treatment (after approximately study Week 8)
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 9 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 9 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 9 years)
Percentage of Participants With AEs
Time frame: Up to 9 years
Nodal Downstaging
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: Neo-adjuvant: pre-dose & 2 hours post-dose on Day 1 of Cycles 1 & 2; Pre-surgery (before Week 8): pre-dose; Adjuvant treatment: pre-dose & 2 hours post-dose on Day 1 of Cycles 1-6, pre-dose on Day 1 of Cycle 9 (each cycle=28 days);
Eligibility criteria
Study locations (38)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
City of Hope - Orange County Lennar Foundation Cancer Center
Irvine, California, 92618
USC Norris Cancer Center
Los Angeles, California, 90033
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of California Los Angeles - Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
Orange, California, 92868
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
UCSF Helen Diller Family CCC
San Francisco, California, 94158
University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)
Aurora, Colorado, 80045
Yale Cancer Center
New Haven, Connecticut, 06511
MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
Washington D.C., District of Columbia, 20007
Moffitt Cancer Center
Tampa, Florida, 33612
Northwestern University
Chicago, Illinois, 60611
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Boston Medical Center
Boston, Massachusetts, 02118
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Michigan
Ann Arbor, Michigan, 48109
Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Mayo Clinic
Rochester, Minnesota, 55905
Ellis Fischel Cancer Center
Columbia, Missouri, 65201
Siteman Cancer Center - Washington University Medical Campus
St Louis, Missouri, 63108
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44016
Ohio State University
Columbus, Ohio, 43210
AHN Cancer Institute ? Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Baptist Clinical Research Institute
Memphis, Tennessee, 38120
Tennessee Oncology - Nashville
Nashville, Tennessee, 37203
Kelsey Seybold Clnic
Houston, Texas, 77025
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4008
Baylor College of Medicine
Houston, Texas, 77030
Lumi Research
Kingwood, Texas, 77339
Virginia Cancer Specialists (Fairfax) - USOR
Fairfax, Virginia, 22031
Seattle Cancer Care Alliance
Seattle, Washington, 98109