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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04302025
• Other study ID #: ML41591
• Status: Recruiting
• Phase: Phase 2
• Start date: November 6, 2020
• Est. completion date: March 6, 2029

Study information

• Verified date: April 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: ML41591 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: March 6, 2029
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Alectinib
Participants will receive oral alectinib twice per day (BID)
• Entrectinib
Participants will receive oral entrectinib daily
• Vemurafenib (Enrollment closed)
Participants will receive oral vemurafenib BID
• Cobimetinib (Enrollment closed)
Participants will receive oral cobimetinib daily
• Pralsetinib (Enrollment closed)
Participants will receive oral pralsetinib daily
• Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion
• 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

Drug:
• Chemotherapy
Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician
• Divarasib
Participants in the KRAS G12C cohort will receive divarasib for approximately 8 weeks until the day before surgery.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute; Brigham and Women's Cancer Center	Boston	Massachusetts
United States	Northwestern University; Robert H. Lurie Comp Can Ctr	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	University of Missouri Health Care; Ellis Fischel Cancer Center	Columbia	Missouri
United States	Ohio State University; Hemat/Onc	Columbus	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	HCA Midwest Health	Kansas City	Missouri
United States	Lumi Research	Kingwood	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA Hematology Oncology	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Baptist Clinical Research Institute	Memphis	Tennessee
United States	Sylvester Comprehensive Cancer Center - Deerfield Beach	Miami	Florida
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Laura and ISAAC Perlmutter Cancer Center at NYU Langone.	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange	Orange	California
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine; Sitemann Cancer Center	Saint Louis	Missouri
United States	UCSF	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tyrosine kinase inhibitor (TKI) cohort: Proportion of Participants with Major Pathologic Response (MPR)	MPR is defined as	After surgical resection (approximately study Week 8)
Primary	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	After surgical resection (approximately study Week 8)
Primary	KRAS cohort: Percentage of participants with 3-5 grade Adverse Events		After surgical resection (approximately study Week 8)
Primary	KRAS cohort: Percentage of participants without delays of surgery due to treatment-related adverse events as reported by the investigator		After surgical resection (approximately study Week 8)
Secondary	Proportion of Participants with MPR	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	After surgical resection (approximately study Week 8)
Secondary	Proportion of Participants with pCR	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	After surgical resection (approximately study Week 8)
Secondary	Pathological Regression Based on Weighted % Viable Tumor Cell Assessment		After surgical resection (approximately study Week 8)
Secondary	Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1		After neoadjuvant treatment (after approximately study Week 8)
Secondary	Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories	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	At the time of surgical resection (approximately study Week 8)
Secondary	Disease-Free Survival (DFS)		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)
Secondary	Event-Free Survival (EFS)		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)
Secondary	Overall Survival (OS)		From the first dose of study medication to death from any cause, through the end of the study (up to 8 years)
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 8 years
Secondary	Nodal downstaging, defined as percentage of patients with reduced stages in mediastinal nodes at surgery		After surgical resection (approximately study Week 8)
Secondary	Circulating tumor DNA ctDNA Clearance Rate		Prior to surgery (before study Week 8)
Secondary	KRAS G12C cohort: Plasma concentration of divarasib at specified timepoints		Cycle 1 Day 1, Cycle 2 Day 1 (Cycle= 28 days)