A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

Официальное название

A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

Обзор

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).

Вмешательства

• Препарат Divarasib
  Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
• Препарат Pembrolizumab
  Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
• Препарат Carboplatin
  Participants will receive IV carboplatin Q3W for four 21-day cycles.
• Препарат Cisplatin
  Participants will receive IV cisplatin Q3W for four 21-day cycles.
• Препарат Pemetrexed
  Participants will receive IV pemetrexed Q3W.

Первичные конечные точки

• Percentage of Participants with Adverse Events (AEs) [Срок оценки: Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years)]

Вторичные конечные точки (11)

• Objective Response Rate (ORR) [Срок оценки: Approximately 5 years]
• Duration of Response (DOR) [Срок оценки: Approximately 5 years]
• Progression Free Survival (PFS) [Срок оценки: Approximately 5 years]
• Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Срок оценки: Approximately 5 years]
• Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE [Срок оценки: Baseline up to approximately 5 years]
• Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria [Срок оценки: Approximately 5 years]
• Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE [Срок оценки: Approximately 5 years]
• Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46) [Срок оценки: Approximately 5 years]
• Plasma or CSF Concentration of Divarasib at Specified Timepoints [Срок оценки: Approximately 5 years]
• Identification of Divarasib Recommended Dose [Срок оценки: Approximately 5 years]
• Central Nervous System (CNS) Response [Срок оценки: Approximately 5 years]

Критерии участия

Критерии включения

• Confirmation of Biomarker eligibility
• Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
• No prior systemic treatment for advanced unresectable or metastatic NSCLC
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment.

Критерии исключения

• Known concomitant second oncogenic driver with available targeted treatment
• Squamous cell histology NSCLC
• Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C)
• Prior treatment with a KRAS G12C inhibitor
• Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment
• History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
• Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
• Co-morbid condition that is an absolute contraindication to treatment with corticosteroids
• Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation.
• Participants with brain metastases for whom complete surgical resections is clinically appropriate

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 16 центров

• City of Hope National Medical Center — Duarte
• City of Hope - Seacliff — Huntington Beach
• City of Hope at Irvine Lennar — Irvine
• UCSD Moores Cancer Center — La Jolla
• City of Hope - Long Beach Elm — Long Beach
• Yale Cancer Center — New Haven
• Florida Cancer Specialists - SOUTH - SCRI - PPDS — Fort Myers
• Florida Cancer Specialists - NORTH - SCRI - PPDS — St. Petersburg
• … и ещё 8 центров

Испания · 6 центров

• ICO Badalona-H.U. Germans Trias i Pujol — Badalona
• Vall d?Hebron Institute of Oncology (VHIO), Barcelona — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Clinico Universitario de Valencia — Valencia

Япония · 5 центров

• National Cancer Center Hospital East — Chiba
• Kindai University Hospital — Osaka
• National Cancer Center Hospital — Tokyo
• The Cancer Institute Hospital of JFCR — Tokyo
• Wakayama Medical University Hospital — Wakayama

South Korea · 5 центров

• Pusan National University Hospital — Busan
• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul
• Korea University Guro Hospital — Seoul

Бельгия · 4 центра

• Cliniques Universitaires St-Luc — Brussels
• Jessa Zkh (Campus Virga Jesse) — Hasselt
• Clinique Ste-Elisabeth — Namur
• AZ Delta (Campus Rumbeke) — Roeselare

Италия · 4 центра

• Istituto Nazionale Tumori Fondazione G. Pascale — Naples
• Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Irccs Istituto Nazionale Dei Tumori (Int) — Milan
• A.O. Universitaria S. Luigi Gonzaga — Orbassano

Тайвань · 4 центра

• Taichung Veterans General Hospital — Taichung
• National Cheng Kung University Hospital — Tainan
• National Taiwan Uni Hospital — Taipei
• Chang Gung Medical Foundation - Linkou — Taoyuan

Аргентина · 3 центра

• Hospital Britanico — Buenos Aires
• Clinica Adventista Belgrano — Ciudad Autonoma Buenos Aires
• Centro Oncologico Riojano Integral (CORI) — La Rioja

Австралия · 3 центра

• Concord Repatriation General Hospital — Concord
• Peter MacCallum Cancer Centre — Melbourne
• Alfred Health — Melbourne

Канада · 3 центра

• Ottawa Hospital Regional Cancer Centre — Ottawa
• Princess Margaret Cancer Center — Toronto
• Jewish General Hospital — Montreal

Китай · 3 центра

• Hunan Cancer Hospital — Чанша
• Harbin Medical University Cancer Hospital — Харбин
• Shanghai Pulmonary Hospital — Шанхай

Израиль · 3 центра

• Rambam Medical Center — Haifa
• Rabin MC — Petah Tikva
• Tel Aviv Sourasky Medical Ctr — Tel Aviv

Польша · 3 центра

• Uniwersyteckie Centrum Kliniczne — Gda?sk
• Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II — Krakow
• Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie — Olsztyn

Бразилия · 2 центра

• Hospital de Cancer de Barretos — Barretos
• Instituto do Cancer do Estado de Sao Paulo - ICESP — São Paulo

Нидерланды · 2 центра

• NKI The Netherlands Cancer Institute — Amsterdam
• UMC St Radboud — Nijmegen

Швейцария · 2 центра

• Universitätsspital Basel — Basel
• Inselspital Bern — Bern

Великобритания · 2 центра

• Beatson West of Scotland Cancer Centre — Glasgow
• Barts & London School of Med — London

Швеция · 1 центр

• Sahlgrenska University Hospital — Gothenburg

Идентификаторы

NCT: NCT05789082 · BO44426 · 2022-003048-28 · 2023-507171-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗