A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib 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

Last updated: March 26, 2025
Sponsor: Hoffmann-La Roche
Overall Status: Active - Recruiting

Phase

1/2

Condition

Non-small Cell Lung Cancer

Treatment

Pembrolizumab

GDC-6036

Pemetrexed

Clinical Study ID

NCT05789082
BO44426
2022-003048-28
2023-507171-22-00
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of divarasib combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Confirmation of Biomarker eligibility

  • Pre-treatment tumor tissue along with an associated pathology report is required forall participants enrolled on study. Representative tumor specimens must be informalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshlycut, serial slides. Although 15 slides are required, if only 10 slides areavailable, the participant may be eligible for the study following consultation withthe Sponsor.

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

  • Histologically or cytologically documented locally advanced unresectable ormetastatic NSCLC that is not eligible for curative surgery and/or definitivechemoradiotherapy

  • No prior systemic treatment for advanced unresectable or metastatic NSCLC

  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion

Exclusion Criteria:

  • Known concomitant second oncogenic driver with available targeted treatment

  • Squamous cell histology NSCLC

  • Symptomatic, untreated, or actively progressing central nervous system (CNS)metastases

  • Prior treatment with a KRAS G12C inhibitor

  • Known hypersensitivity to any of the components of divarasib or pembrolizumab; orknown hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)

  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitisobliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence ofactive pneumonitis, active tuberculosis, significant cardiovascular disease within 3months prior to initiation of study treatment

  • History of malignancy other than NSCLC within 5 years prior to initiation of studytreatment, with the exception of malignancies with a negligible risk of metastasisor death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma insitu of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductalbreast carcinoma in situ, or Stage I uterine cancer

  • Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascitesrequiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia

Study Design

Total Participants: 240
Treatment Group(s): 6
Primary Treatment: Pembrolizumab
Phase: 1/2
Study Start date:
June 20, 2023
Estimated Completion Date:
May 20, 2027

Connect with a study center

  • Hospital Britanico

    Buenos Aires, C1280AEB
    Argentina

    Active - Recruiting

  • Hospital Britanico; Oncologia

    Buenos Aires, C1280AEB
    Argentina

    Active - Recruiting

  • Clinica Adventista Belgrano

    Ciudad Autonoma Buenos Aires, C1430EGF
    Argentina

    Active - Recruiting

  • Clinica Adventista Belgrano; Oncology

    Ciudad Autonoma Buenos Aires, C1430EGF
    Argentina

    Active - Recruiting

  • Centro Oncologico Riojano Integral (CORI)

    La Rioja, F5300COE
    Argentina

    Active - Recruiting

  • Concord Repatriation General Hospital

    Concord, New South Wales 2139
    Australia

    Active - Recruiting

  • Concord Repatriation General Hospital; Concord Cancer Centre

    Concord, New South Wales 2139
    Australia

    Active - Recruiting

  • Alfred Health

    Melbourne, Victoria 3004
    Australia

    Active - Recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria 3000
    Australia

    Active - Recruiting

  • Peter MacCallum Cancer Centre; Medical Oncology

    Melbourne, Victoria 3000
    Australia

    Active - Recruiting

  • Cliniques Universitaires St-Luc

    Bruxelles, 1200
    Belgium

    Active - Recruiting

  • Jessa Zkh (Campus Virga Jesse)

    Hasselt, 3500
    Belgium

    Active - Recruiting

  • Clinique Ste-Elisabeth

    Namur, 5000
    Belgium

    Active - Recruiting

  • AZ Delta (Campus Rumbeke)

    Roeselare, 8800
    Belgium

    Active - Recruiting

  • Crio - Centro Regional Integrado de Oncologia

    Fortaleza, CE 60336-232
    Brazil

    Site Not Available

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, RS 90040-373
    Brazil

    Site Not Available

  • Hospital de Cancer de Barretos

    Barretos, São Paulo 14784-400
    Brazil

    Active - Recruiting

  • Instituto do Cancer do Estado de Sao Paulo - ICESP

    Sao Paulo, São Paulo 01246-000
    Brazil

    Active - Recruiting

  • Princess Margaret Cancer Center

    Toronto, Ontario M5G 1Z5
    Canada

    Site Not Available

  • Jewish General Hospital

    Montreal, Quebec H3T 1E2
    Canada

    Active - Recruiting

  • Hunan Cancer Hospital

    Changsha CITY, 410013
    China

    Site Not Available

  • Harbin Medical University Cancer Hospital

    Harbin, 150081
    China

    Site Not Available

  • Shanghai Pulmonary Hospital

    Shanghai, 200433
    China

    Site Not Available

  • Rambam Medical Center

    Haifa, 3109601
    Israel

    Active - Recruiting

  • Rambam Medical Center; Oncology

    Haifa, 3109601
    Israel

    Active - Recruiting

  • Rabin MC

    Petach Tikva, 4941492
    Israel

    Active - Recruiting

  • Rabin MC; Davidof Center - Oncology Institute

    Petach Tikva, 4941492
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Ctr

    Tel Aviv, 6423906
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Ctr; Oncology

    Tel Aviv, 6423906
    Israel

    Active - Recruiting

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Napoli, Campania 80131
    Italy

    Active - Recruiting

  • Policlinico Universitario Agostino Gemelli IRCCS

    Roma, Lazio 00168
    Italy

    Site Not Available

  • Policlinico Universitario Agostino Gemelli IRCCS; UOS Fase 1

    Roma, Lazio 00168
    Italy

    Active - Recruiting

  • Irccs Istituto Nazionale Dei Tumori (Int)

    Milano, Lombardia 20133
    Italy

    Active - Recruiting

  • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

    Milano, Lombardia 20133
    Italy

    Active - Recruiting

  • A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica

    Orbassano, Piemonte 10043
    Italy

    Active - Recruiting

  • A.O. Universitaria S. Luigi Gonzaga

    Orbassano, Piemonte 10043
    Italy

    Active - Recruiting

  • Pusan National University Hospital

    Busan, 49241
    Korea, Republic of

    Active - Recruiting

  • Asan Medical Center

    Seoul, 05505
    Korea, Republic of

    Active - Recruiting

  • Korea University Guro Hospital

    Seoul, 08308
    Korea, Republic of

    Active - Recruiting

  • Samsung Medical Center

    Seoul, 06351
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Hospital

    Seoul, 03080
    Korea, Republic of

    Active - Recruiting

  • NKI The Netherlands Cancer Institute

    Amsterdam, 1066 CX
    Netherlands

    Site Not Available

  • UMC St Radboud

    Nijmegen, 6525 GA
    Netherlands

    Active - Recruiting

  • Uniwersyteckie Centrum Kliniczne

    Gda?sk, 80-214
    Poland

    Active - Recruiting

  • Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz

    Gda?sk, 80-214
    Poland

    Active - Recruiting

  • Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

    Kraków, 31-202
    Poland

    Active - Recruiting

  • Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II; Oddzia? Onkologiczny

    Kraków, 31-202
    Poland

    Active - Recruiting

  • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

    Olsztyn, 10-357
    Poland

    Site Not Available

  • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii

    Olsztyn, 10-357
    Poland

    Active - Recruiting

  • ICO Badalona-H.U. Germans Trias i Pujol

    Badalona, Barcelona 08916
    Spain

    Active - Recruiting

  • NEXT Oncology-Hospital Quironsalud Madrid

    Pozuelo de Alarcon, Madrid 28223
    Spain

    Site Not Available

  • Vall d?Hebron Institute of Oncology (VHIO), Barcelona

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, 28009
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, 28041
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio; Servicio de Oncologia

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010
    Spain

    Site Not Available

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010
    Spain

    Active - Recruiting

  • Sahlgrenska University Hospital

    Göteborg, 411 36
    Sweden

    Active - Recruiting

  • Sahlgrenska University Hospital; Sahlgrenska Clinical Trial unit / Department of Oncology

    Göteborg, 413 45
    Sweden

    Active - Recruiting

  • Universitätsspital Basel

    Basel, 4031
    Switzerland

    Site Not Available

  • Universitätsspital Basel; Oncology - Klinische Forschung

    Basel, 4031
    Switzerland

    Site Not Available

  • Inselspital Bern

    Bern, 3010
    Switzerland

    Active - Recruiting

  • Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit

    Bern, 3010
    Switzerland

    Active - Recruiting

  • Inselspital Bern; Universitätsklinik für medizinische Onkologie

    Bern, 3010
    Switzerland

    Active - Recruiting

  • National Cheng Kung University Hospital; Internal Medicine

    North Dist., 70403
    Taiwan

    Site Not Available

  • Taichung Veterans General Hospital

    Taichung, 407
    Taiwan

    Active - Recruiting

  • Taichung Veterans General Hospital; Dept of Internal Medicine

    Taichung, 407
    Taiwan

    Active - Recruiting

  • National Cheng Kung University Hospital

    Tainan,
    Taiwan

    Active - Recruiting

  • National Taiwan Uni Hospital

    Taipei, 100
    Taiwan

    Active - Recruiting

  • National Taiwan Uni Hospital; Internal Medicine

    Taipei, 100
    Taiwan

    Active - Recruiting

  • Chang Gung Medical Foundation - Linkou

    Taoyuan, 333
    Taiwan

    Site Not Available

  • Chang Gung Medical Foundation - Linkou; Chest Dept

    Taoyuan, 333
    Taiwan

    Site Not Available

  • Adana City Hospital, Medical Oncology

    Adana, 01060
    Turkey

    Site Not Available

  • Ankara Bilkent City Hospital

    Ankara, 06490
    Turkey

    Site Not Available

  • Koc University Hospital; Oncology

    Istanbul,
    Turkey

    Site Not Available

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN
    United Kingdom

    Active - Recruiting

  • Barts & London School of Med

    London, EC1A 7BE
    United Kingdom

    Active - Recruiting

  • Barts & London School of Med; Medical Oncology

    London, EC1A 7BE
    United Kingdom

    Active - Recruiting

  • City of Hope National Medical Center

    Duarte, California 91010
    United States

    Active - Recruiting

  • City of Hope - Seacliff

    Huntington Beach, California 92648
    United States

    Active - Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California 92618
    United States

    Active - Recruiting

  • UCSD Moores Cancer Center

    La Jolla, California 92093
    United States

    Active - Recruiting

  • Yale Cancer Center

    New Haven, Connecticut 06520
    United States

    Active - Recruiting

  • NYU Langone Hospital - Long Island

    Mineola, New York 11501
    United States

    Active - Recruiting

  • Mount SInai Medical Center

    New York, New York 10029
    United States

    Active - Recruiting

  • NYU Cancer Center

    New York, New York 10016
    United States

    Active - Recruiting

  • NYU Cancer Center; NYU Cancer Institute

    New York, New York 10016
    United States

    Active - Recruiting

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • MD Anderson Cancer Center; Oncology

    Houston, Texas 77030
    United States

    Active - Recruiting

  • Oncology & Hematology Associates of Southwest Virginia, Inc

    Blacksburg, Virginia 24060
    United States

    Active - Recruiting

  • Virginia Oncology Associates

    Norfolk, Virginia 23502
    United States

    Active - Recruiting

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