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Search / Trial NCT06497556

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

Launched by HOFFMANN-LA ROCHE · Jul 5, 2024

Trial Information

Current as of June 27, 2025

Recruiting

Keywords

Advanced Non Small Cell Lung Cancer Kras G12 Lung Cancer Advanced Lung Cancer Metastatic Lung Cancer Divarasib Kras G12 C Inhibitor Kras G12 C Positive Kras Mutation Kras G12 C Mutation Lung Cancer Mutation

ClinConnect Summary

This clinical trial is studying a new treatment called divarasib for patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation known as KRAS G12C. The goal is to see if divarasib is safer and more effective than currently approved treatments like sotorasib or adagrasib. To participate, individuals must have already received at least one previous treatment for their cancer, have measurable disease, and provide a tumor sample that shows the KRAS G12C mutation.

Eligible participants should be between the ages of 65 and 74, have a good performance status (meaning they can carry out daily activities), and expect to live for at least 12 weeks. Throughout the trial, participants will receive regular check-ups to monitor their health and the effects of the treatment. This study is currently recruiting participants, and it's important to note that anyone with certain health conditions or a history of specific cancers may not be eligible. If you or a family member are interested in learning more about participating, consider discussing it with your healthcare provider.

Gender

ALL

Eligibility criteria

  • 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

About Hoffmann La Roche

Hoffmann-La Roche, commonly known as Roche, is a global leader in biotechnology and pharmaceuticals, committed to advancing healthcare through innovative research and development. With a strong focus on oncology, immunology, infectious diseases, and central nervous system disorders, Roche leverages cutting-edge science to deliver transformative therapies and diagnostics. The company is dedicated to improving patient outcomes by conducting rigorous clinical trials and collaborating with healthcare professionals and organizations worldwide. Roche's unwavering commitment to precision medicine and personalized healthcare positions it at the forefront of the industry, driving progress in the quest for effective treatments and improved patient care.

Locations

New York, New York, United States

New York, New York, United States

Lyon, , France

Boston, Massachusetts, United States

Sioux Falls, South Dakota, United States

Little Rock, Arkansas, United States

Liverpool, New South Wales, Australia

Paris, , France

Zaragoza, , Spain

Fort Myers, Florida, United States

Hong Kong, , Hong Kong

Boston, Massachusetts, United States

Miami, Florida, United States

Columbus, Ohio, United States

Houston, Texas, United States

Chicago, Illinois, United States

Chapel Hill, North Carolina, United States

Orange, California, United States

Portland, Oregon, United States

Nottingham, , United Kingdom

Barcelona, , Spain

Halle, , Germany

Ann Arbor, Michigan, United States

San Francisco, California, United States

Greenville, North Carolina, United States

Bruxelles, , Belgium

Montreal, Quebec, Canada

Lexington, Kentucky, United States

Khon Kaen, , Thailand

Valencia, , Spain

Essen, , Germany

Helsinki, , Finland

Fukuoka, , Japan

Niigata, , Japan

Okayama, , Japan

Herlev, , Denmark

Taipei, , Taiwan

Blackpool, , United Kingdom

Montpellier, , France

Elizabeth Vale, South Australia, Australia

Nashville, Tennessee, United States

Tokyo, , Japan

Athens, Georgia, United States

Hong Kong, , Hong Kong

Kaohsiung, , Taiwan

Porto Alegre, Rs, Brazil

Glasgow, , United Kingdom

Lille, , France

Muncie, Indiana, United States

Edegem, , Belgium

Hemer, , Germany

Seongnam Si, , Korea, Republic Of

Seoul, , Korea, Republic Of

Seoul, , Korea, Republic Of

Berlin, , Germany

Oldenburg, , Germany

Melbourne, Victoria, Australia

Leeds, , United Kingdom

Bron, , France

Madrid, , Spain

Bydgoszcz, , Poland

Brussel, , Belgium

Lublin, , Poland

Manchester, , United Kingdom

Busan, , Korea, Republic Of

Cambridge, , United Kingdom

West Palm Beach, Florida, United States

San Francisco, California, United States

Shizuoka, , Japan

Buenos Aires, , Argentina

Aalst, , Belgium

Los Angeles, California, United States

Immenhausen, , Germany

New Haven, Connecticut, United States

Warszawa, , Poland

Liège, , Belgium

Barretos, Sp, Brazil

Angers, , France

Pittsburgh, Pennsylvania, United States

Esslingen, , Germany

Lübeck, , Germany

Pessac, , France

Regensburg, , Germany

Heidelberg, , Germany

Großhansdorf, , Germany

Hasselt, , Belgium

Scarborough, Maine, United States

Incheon, , Korea, Republic Of

Barcelona, , Spain

Breda, , Netherlands

Grand Rapids, Michigan, United States

Toulouse, , France

Songkhla, , Thailand

Berlin, , Germany

Tokyo, , Japan

Jeollanam Do, , Korea, Republic Of

Salvador, Ba, Brazil

Strasbourg, , France

Buenos Aires, , Argentina

Jacksonville, Florida, United States

Seoul, , Korea, Republic Of

Pinehurst, North Carolina, United States

'S Hertogenbosch, , Netherlands

Wilrijk, , Belgium

München, , Germany

Hokkaido, , Japan

Braunschweig, , Germany

Aarhus N, , Denmark

Seoul, , Korea, Republic Of

Roeselare, , Belgium

Guadalajara, Jalisco, Mexico

Cottingham, , United Kingdom

Savannah, Georgia, United States

Esslingen, , Germany

Gdansk, , Poland

London, , United Kingdom

Arnhem, , Netherlands

Malaga, , Spain

Brest, , France

Daegu, , Korea, Republic Of

Regensburg, , Germany

Gävle, , Sweden

Osaka, , Japan

Kaohsiung City, , Taiwan

Taipei, , Taiwan

Sao Jose Do Rio Preto, Sp, Brazil

Madrid, , Spain

Braga, , Portugal

Daegu, , Korea, Republic Of

Cheongju Si, , Korea, Republic Of

Birtinya, Queensland, Australia

Toronto, Ontario, Canada

Parma, Emilia Romagna, Italy

Sutton, , United Kingdom

Saint Quentin, , France

Saint Petersburg, Florida, United States

Memphis, Tennessee, United States

Mont Godinne, , Belgium

Fort Worth, Texas, United States

Hong Kong, , Hong Kong

Halle, , Germany

Homburg, , Germany

Pisa, Toscana, Italy

Saint Augustine, Florida, United States

Eugene, Oregon, United States

Darlinghurst, New South Wales, Australia

Zwolle, , Netherlands

Bergamo, Lombardia, Italy

Gyeonggi Do, , Korea, Republic Of

Gyeongsangnam Do, , Korea, Republic Of

Stoke On Trent, , United Kingdom

Homburg, , Germany

Novara, Piemonte, Italy

Wakayama, , Japan

Gauting, , Germany

Seville, Sevilla, Spain

Genova, Liguria, Italy

Poznan, , Poland

Aarhus N, , Denmark

Ehime, , Japan

Hong Kong, , Hong Kong

Bron, , France

Harderwijk, , Netherlands

Bangkok, , Thailand

Cardiff, , United Kingdom

Hospitalet De Llobregat, Barcelona, Spain

Darlinghurst, New South Wales, Australia

Spartanburg, South Carolina, United States

Essen, , Germany

Würzburg, , Germany

Omaha, Nebraska, United States

Münster, , Germany

Sint Niklaas, , Belgium

Bronx, New York, United States

Wien, , Austria

Sao Paulo, , Brazil

Rio De Janeiro, Rj, Brazil

St Leonards, New South Wales, Australia

Ciudad Autonoma Buenos Aires, , Argentina

Rio De Janeiro, , Brazil

Rosario, , Argentina

Birtinya, Queensland, Australia

Herning, , Denmark

Porto Alegre, Rio Grande Do Sul, Brazil

Leidschendam, , Netherlands

Heroica Puebla De Zaragoza, Puebla, Mexico

New York, New York, United States

Radom, , Poland

Palermo, Sicilia, Italy

Toulon, , France

Faliro, , Greece

Hsinchu City, , Taiwan

Poznan, , Poland

Methuen, Massachusetts, United States

Los Angeles, California, United States

Ciudad Autonoma Buenos Aires, , Argentina

Lisboa, , Portugal

Gilbert, Arizona, United States

Longview, Texas, United States

New Hyde Park, New York, United States

Porto Alegre, Rs, Brazil

Olsztyn, , Poland

Bologna, Emilia Romagna, Italy

?ód?, , Poland

Strasbourg, , France

Udine, Friuli Venezia Giulia, Italy

Columbus, Ohio, United States

Reno, Nevada, United States

Sao Jose Do Rio Preto, São Paulo, Brazil

Singapore, , Singapore

Thessaloniki, , Greece

Taipei, , Taiwan

Foxboro, Massachusetts, United States

Ciudad De México, , Mexico

Porto Alegre, Rs, Brazil

Miyagi, , Japan

Sao Paulo, São Paulo, Brazil

Des Moines, Iowa, United States

Taichung, , Taiwan

Brasilia, Df, Brazil

Sao Paulo, Sp, Brazil

Brampton, Ontario, Canada

Maumee, Ohio, United States

Warszawa, , Poland

Wien, , Austria

Santiago De Querétaro, Queretaro, Mexico

Elizabeth Vale, South Australia, Australia

Gävle, , Sweden

Taichung, , Taiwan

Sao Paulo, São Paulo, Brazil

Bari, Puglia, Italy

Porto, , Portugal

Lublin, , Poland

Olsztyn, , Poland

Wroc?Aw, , Poland

Porto, , Portugal

Torquay, , United Kingdom

Salvador, Bahia, Brazil

Roma, Lazio, Italy

Taoyuan, , Taiwan

Ravenna, Emilia Romagna, Italy

Firenze, Toscana, Italy

Barretos, São Paulo, Brazil

Kraków, , Poland

Ciudad Autonoma Buenos Aires, , Argentina

Turku, , Finland

Warszawa, , Poland

Porto Alegre, Rio Grande Do Sul, Brazil

Larissa, , Greece

Louisville, Kentucky, United States

Shirley, New York, United States

Chattanooga, Tennessee, United States

Wien, , Austria

Brasilia, Distrito Federal, Brazil

Campo Grande, Mato Grosso Do Sul, Brazil

Porto Alegre, Rio Grande Do Sul, Brazil

Nice, , France

Berlin, , Germany

Essen, , Germany

Kiel, , Germany

Köln, , Germany

Löwenstein, , Germany

Mannheim, , Germany

Athens, , Greece

Athens, , Greece

Thessaloniki, , Greece

Shatin, , Hong Kong

Catanzaro, Calabria, Italy

Rozzano (Mi), Lombardia, Italy

Sassari, Sardegna, Italy

Palermo, Sicilia, Italy

Padova, Veneto, Italy

Saltillo, Coahuila, Mexico

?ód?, , Poland

Coimbra, , Portugal

Singapore, , Singapore

Bangkok, , Thailand

London, , United Kingdom

Kuopio, , Finland

Detroit, Michigan, United States

Aalst, , Belgium

Colorado Springs, Colorado, United States

Bay Pines, Florida, United States

Richmond, Virginia, United States

Waukee, Iowa, United States

Shreveport, Louisiana, United States

Barretos, , Brazil

Sao Paulo, , Brazil

Sao Jose Do Rio Preto, , Brazil

Patients applied

0 patients applied

Trial Officials

Clinical Trials

Study Director

Hoffmann-La Roche

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported