Clinical trial NCT04302025: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-10
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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 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

Primary outcomes:
measure: Tyrosine kinase inhibitor (TKI) cohort: Proportion of Participants with Major Pathologic Response (MPR)
timeFrame: After surgical resection (approximately study Week 8)
measure: Checkpoint inhibitor (CPI) cohort: Pathological complete response (pCR)
timeFrame: After surgical resection (approximately study Week 8)
measure: KRAS cohort: Percentage of participants with 3-5 grade Adverse Events
timeFrame: After surgical resection (approximately study Week 8)
measure: KRAS cohort: Percentage of participants without delays of surgery due to treatment-related adverse events as reported by the investigator
timeFrame: After surgical resection (approximately study Week 8)
Secondary outcomes:
measure: Proportion of Participants with MPR
timeFrame: After surgical resection (approximately study Week 8)
measure: Proportion of Participants with pCR
timeFrame: After surgical resection (approximately study Week 8)
measure: Pathological Regression Based on Weighted % Viable Tumor Cell Assessment
timeFrame: After surgical resection (approximately study Week 8)
measure: Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1
timeFrame: After neoadjuvant treatment (after approximately study Week 8)
measure: Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories
timeFrame: At the time of surgical resection (approximately study Week 8)
measure: Disease-Free Survival (DFS)
timeFrame: 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)
measure: Event-Free Survival (EFS)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From the first dose of study medication to death from any cause, through the end of the study (up to 8 years)
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 8 years
measure: Nodal downstaging, defined as percentage of patients with reduced stages in mediastinal nodes at surgery
timeFrame: After surgical resection (approximately study Week 8)
measure: Circulating tumor DNA ctDNA Clearance Rate
timeFrame: Prior to surgery (before study Week 8)
measure: KRAS G12C cohort: Plasma concentration of divarasib at specified timepoints
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1 (Cycle= 28 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Irvine
country: United States
facility: City of Hope - Orange County Lennar Foundation Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles - Jonsson Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family CCC
state: California
city: Aurora
country: United States
facility: University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: DeKalb
country: United States
facility: Northwestern Medicine Cancer Center Kishwaukee
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - Washington University Medical Campus
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: AHN Cancer Institute ? Allegheny General Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: Baptist Clinical Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Houston
country: United States
facility: Kelsey Seybold Clnic
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists (Fairfax) - USOR
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: