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Clinical Trials in the UK / NCT06497556
Active, not recruiting Phase 3

A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer

NCT06497556 · tracked via the Priya Life Science UK tracker
Sponsor
Hoffmann-La Roche
Phase
Phase 3
Started
2024-09-23
Last updated
2026-09-16

Condition(s) studied

Non-Small Cell Lung CancerKRAS G12C Lung Cancer

Investigational drug(s) / intervention(s)

DivarasibSotorasibAdagrasib

Divarasib: Divarasib will be administered orally QD

Sotorasib: Sotorasib will be administered orally QD

Adagrasib: Adagrasib will be administred orally BID

Study summary

The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation * Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Documentation of the presence of a KRAS G12C mutation * Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of \>= 12 weeks Exclusion Criteria: * Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib * Malabsorption syndrome or other condition that would interfere with enteral absorption * Known concomitant second oncogenic driver * Mixed small-cell lung cancer or large cell neuroendocrine histology * Known and untreated, or active central nervous system (CNS) metastases * Leptomeningeal disease or carcinomatous meningitis * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently * Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1 * Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor * More than 30 Gy of radiotherapy to the lung within 6 months of randomization * Uncontrolled tumor-related pain * Unresolved toxicities from prior anticancer therapy * History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

Primary outcome measure(s)

Trial sites (151)

FacilityCityRegionStatus
Banner Health MD Anderson AZ Gilbert Arizona
Los Angeles Cancer Network Los Angeles California
UCLA Hematology / Oncology Clinic Los Angeles California
University of California, San Francisco San Francisco California
Yale Cancer Center New Haven Connecticut
University of Miami Miami Florida
Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg) St. Petersburg Florida
University of Chicago Medical Center Chicago Illinois
New England Cancer Specialists Westbrook Maine
Dana Farber Cancer Institute Boston Massachusetts
University of Michigan Ann Arbor Michigan
Cancer and Hematology Centers of Western Michigan Grand Rapids Michigan
Minnesota Oncology Edina Edina Minnesota
Columbia University Medical Center New York New York
Taylor Cancer Research Center Maumee Ohio
Oncology Associates of Oregon, P.C Eugene Oregon
Oregon Health & Science University Portland Oregon
Fox Chase Cancer Center Philadelphia Pennsylvania
Allegheny Cancer Center Pittsburgh Pennsylvania
Tennessee Oncology, PLLC - Chattanooga Chattanooga Tennessee
Baptist Clinical Research Institute Memphis Tennessee
Tennessee Oncology Nashville Tennessee
JPS Health Network Fort Worth Texas
MD Anderson Cancer Center Houston Texas
Texas Oncology - Northeast Texas Longview Texas
Hospital Britanico Buenos Aires Argentina
Centro Oncologico Korben Ciudad Autonoma Buenos Aires Argentina
Liverpool Hospital Liverpool New South Wales
GenesisCare North Shore St Leonards New South Wales
Sunshine Coast University Hospital Birtinya Queensland
Lyell McEwin Hospital Elizabeth Vale South Australia
Peter Maccallum Cancer Centre Melbourne Victoria
Krankenhaus Nord - Klinik Floridsdorf Vienna Austria
AZORG Campus Aalst-Moorselbaan Aalst Belgium
UZ Brussel Brussels Belgium
Cliniques Universitaires St-Luc Brussels Belgium
UZ Antwerpen Edegem Belgium
Jessa Zkh (Campus Virga Jesse) Hasselt Belgium
CHU de Liège (Sart Tilman) Liège Belgium
CHU UCL Mont-Godinne Mont-godinne Belgium

+ 111 more sites — see the full list on the official registry below.

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 NCT06497556 on ClinicalTrials.gov ↗ ← All trials in the UK