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
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)
Progression-Free Survival (PFS) — Up to approximately 4 years PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)
Trial sites (151)
Facility
City
Region
Status
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.
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.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.