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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Alectinib
  Participants will receive oral alectinib twice per day (BID).
• Препарат Entrectinib
  Participants will receive oral entrectinib daily.
• Препарат Vemurafenib
  Participants will receive oral vemurafenib BID.
• Препарат Cobimetinib
  Participants will receive oral cobimetinib daily.
• Препарат Pralsetinib
  Participants will receive oral pralsetinib daily.
• Препарат Atezolizumab
  Atezolizumab will be administered by intravenous (IV) infusion.
• Препарат SBRT
  Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.
• Процедура Resection
  Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.
• Препарат Chemotherapy
  Participants will receive SOC chemotherapy as determined by the treating physician.
• Препарат Divarasib
  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.

Первичные конечные точки

• Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) [Срок оценки: After surgical resection (approximately study Week 8)]
• Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) [Срок оценки: After surgical resection (approximately study Week 8)]
• KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) [Срок оценки: 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 [Срок оценки: After surgical resection (approximately study Week 8)]

Вторичные конечные точки (11)

• Proportion of Participants With MPR [Срок оценки: After surgical resection (approximately study Week 8)]
• Proportion of Participants With pCR [Срок оценки: After surgical resection (approximately study Week 8)]
• Pathological Regression Based on Weighted % Viable Tumor Cell Assessment [Срок оценки: 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) [Срок оценки: After neoadjuvant treatment (after approximately study Week 8)]
• Disease-free Survival (DFS) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Up to 9 years]
• Nodal Downstaging [Срок оценки: After surgical resection (approximately study Week 8)]
• Circulating tumor DNA (ctDNA) Clearance Rate [Срок оценки: Prior to surgery (before study Week 8)]
• KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints [Срок оценки: 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);]

Критерии участия

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 38 центров

• City of Hope Comprehensive Cancer Center — Duarte
• City of Hope - Orange County Lennar Foundation Cancer Center — Irvine
• USC Norris Cancer Center — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• University of California Los Angeles - Jonsson Comprehensive Cancer Center — Los Angeles
• The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange — Orange
• UC Davis Comprehensive Cancer Center — Sacramento
• UCSF Helen Diller Family CCC — San Francisco
• … и ещё 30 центров

Идентификаторы

NCT: NCT04302025 · ML41591

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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