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Clinical Trials in the UK / NCT05789082
Recruiting Phase 1/2

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

NCT05789082 · tracked via the Priya Life Science UK tracker
Sponsor
Hoffmann-La Roche
Phase
Phase 1/2
Started
2023-06-20
Last updated
2026-09-08

Condition(s) studied

Non-Small Cell Lung Cancer

Investigational drug(s) / intervention(s)

DivarasibPembrolizumabCarboplatinCisplatinPemetrexed

Divarasib: Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.

Pembrolizumab: Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.

Carboplatin: Participants will receive IV carboplatin Q3W for four 21-day cycles.

Cisplatin: Participants will receive IV cisplatin Q3W for four 21-day cycles.

Pemetrexed: Participants will receive IV pemetrexed Q3W.

Study summary

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).

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * 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. Exclusion Criteria: * 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

Primary outcome measure(s)

Trial sites (71)

FacilityCityRegionStatus
City of Hope National Medical Center Duarte California Withdrawn
City of Hope - Seacliff Huntington Beach California Withdrawn
City of Hope at Irvine Lennar Irvine California Withdrawn
UCSD Moores Cancer Center La Jolla California Withdrawn
City of Hope - Long Beach Elm Long Beach California Withdrawn
Yale Cancer Center New Haven Connecticut Recruiting
Florida Cancer Specialists - SOUTH - SCRI - PPDS Fort Myers Florida Recruiting
Florida Cancer Specialists - NORTH - SCRI - PPDS St. Petersburg Florida Recruiting
Florida Cancer Specialists - EAST - SCRI - PPDS West Palm Beach Florida Recruiting
NYU Langone Hospital - Long Island Mineola New York Recruiting
NYU Cancer Center New York New York Recruiting
Mount SInai Medical Center New York New York Recruiting
Montefiore Medical Center - Montefiore Medical Park The Bronx New York Recruiting
MD Anderson Cancer Center Houston Texas Recruiting
Oncology & Hematology Associates of Southwest Virginia, Inc Blacksburg Virginia Recruiting
Virginia Oncology Associates Norfolk Virginia Recruiting
Hospital Britanico Buenos Aires Argentina Recruiting
Clinica Adventista Belgrano Ciudad Autonoma Buenos Aires Argentina Recruiting
Centro Oncologico Riojano Integral (CORI) La Rioja Argentina Recruiting
Concord Repatriation General Hospital Concord New South Wales Completed
Peter MacCallum Cancer Centre Melbourne Victoria Recruiting
Alfred Health Melbourne Victoria Recruiting
Cliniques Universitaires St-Luc Brussels Belgium Recruiting
Jessa Zkh (Campus Virga Jesse) Hasselt Belgium Recruiting
Clinique Ste-Elisabeth Namur Belgium Recruiting
AZ Delta (Campus Rumbeke) Roeselare Belgium Recruiting
Hospital de Cancer de Barretos Barretos São Paulo Recruiting
Instituto do Cancer do Estado de Sao Paulo - ICESP São Paulo São Paulo Recruiting
Ottawa Hospital Regional Cancer Centre Ottawa Ontario Recruiting
Princess Margaret Cancer Center Toronto Ontario Active Not Recruiting
Jewish General Hospital Montreal Quebec Recruiting
Hunan Cancer Hospital Changsha China Active Not Recruiting
Harbin Medical University Cancer Hospital Harbin China Recruiting
Shanghai Pulmonary Hospital Shanghai China Active Not Recruiting
Rambam Medical Center Haifa Israel Recruiting
Rabin MC Petah Tikva Israel Recruiting
Tel Aviv Sourasky Medical Ctr Tel Aviv Israel Recruiting
Istituto Nazionale Tumori Fondazione G. Pascale Naples Campania Withdrawn
Policlinico Universitario Agostino Gemelli IRCCS Rome Lazio Active Not Recruiting
Irccs Istituto Nazionale Dei Tumori (Int) Milan Lombardy Recruiting

+ 31 more sites — see the full list on the official registry below.

On this site

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More Hoffmann-La Roche trials in the UK

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05789082 on ClinicalTrials.gov ↗ ← All trials in the UK