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
Phase 3 – large-scale trial before approval
Conditions:
Non-Small Cell Lung Cancer
KRAS G12C Lung Cancer
Sponsor: Hoffmann-La Roche
trial.available_in:
БГ
Overview
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).
Who can participate
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
Interventions
Divarasib
DRUG
Sotorasib
DRUG
Adagrasib
DRUG
Locations
151
Argentina (2)
Hospital Britanico
Buenos Aires
Centro Oncologico Korben
Ciudad Autonoma Buenos Aires
Australia (5)
Sunshine Coast University Hospital
Birtinya , Queensland
Lyell McEwin Hospital
Elizabeth Vale , South Australia
Liverpool Hospital
Liverpool , New South Wales
Peter Maccallum Cancer Centre
Melbourne , Victoria
GenesisCare North Shore
St Leonards , New South Wales
Austria (1)
Krankenhaus Nord - Klinik Floridsdorf
Vienna
Belgium (10)
AZORG Campus Aalst-Moorselbaan
Aalst
UZ Brussel
Brussels
Cliniques Universitaires St-Luc
Brussels
UZ Antwerpen
Edegem
Jessa Zkh (Campus Virga Jesse)
Hasselt
CHU de Liège (Sart Tilman)
Liège
CHU UCL Mont-Godinne
Mont-godinne
AZ Delta (Campus Rumbeke)
Roeselare
Vitaz
Sint-Niklaas
ZAS Sint Augustinus Wilrijk
Wilrijk
Brazil (5)
Hospital de Cancer de Barretos
Barretos , São Paulo
Hospital Sao Rafael - HSR
Salvador , Estado de Bahia
Hospital de Base de Sao Jose do Rio Preto
São José do Rio Preto , São Paulo
Hospital Sírio-Libanês
São Paulo , São Paulo
Hospital Alemao Oswaldo Cruz
São Paulo , São Paulo
Canada (2)
William Osler Health Centre - Brampton Civic Hospital
Brampton , Ontario
Jewish General Hospital
Montreal , Quebec
Denmark (3)
Aarhus Universitetshospital
Aarhus N
Herlev Hospital
Herlev
Regionshospitalet Gødstrup
Herning
Finland (2)
Helsinki University Central Hospital
Helsinki
Kuopio Uni Hospital
Kuopio
France (12)
CHRU Brest
Brest
Chu Toulouse
Bron
Hopital Louis Pradel
Bron
CHRU Lille
Lille
Centre Leon Berard
Lyon
CHU Montpellier
Montpellier
Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer