A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or 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 (KRAScendo 170)

A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

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

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Divarasib

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO44426 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Recruiting
    • Hospital Britanico
  • Ciudad Autonoma Buenos Aires, Argentina, C1430EGF
    • Recruiting
    • Clinica Adventista Belgrano
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Centro Oncologico Riojano Integral (CORI)
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Completed
      • Concord Repatriation General Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Health
• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires St-Luc
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Zkh (Campus Virga Jesse)
  • Namur, Belgium, 5000
    • Recruiting
    • Clinique Ste-Elisabeth
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta (Campus Rumbeke)
• Brazil
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Recruiting
      • Hospital de Cancer de Barretos
    • São Paulo, São Paulo, Brazil, 01246-000
      • Recruiting
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8M2
      • Recruiting
      • Ottawa Hospital Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 1Z5
      • Active, not recruiting
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
• China
  • Changsha, China, 410013
    • Active, not recruiting
    • Hunan Cancer Hospital
  • Harbin, China, 150081
    • Recruiting
    • Harbin Medical University Cancer Hospital
  • Shanghai, China, 200433
    • Active, not recruiting
    • Shanghai Pulmonary Hospital
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin MC
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Ctr
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Withdrawn
      • Istituto Nazionale Tumori Fondazione G. Pascale
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Active, not recruiting
      • Policlinico Universitario Agostino Gemelli IRCCS
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Recruiting
      • Irccs Istituto Nazionale Dei Tumori (Int)
  • Piedmont
    • Orbassano, Piedmont, Italy, 10043
      • Recruiting
      • A.O. Universitaria S. Luigi Gonzaga
• Japan
  • Chiba, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
  • Osaka, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • Recruiting
    • The Cancer Institute Hospital of JFCR
  • Wakayama, Japan, 641-8510
    • Recruiting
    • Wakayama Medical University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Active, not recruiting
    • NKI The Netherlands Cancer Institute
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • UMC St Radboud
• Poland
  • Gda?sk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 31-202
    • Recruiting
    • Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II
  • Olsztyn, Poland, 10-357
    • Active, not recruiting
    • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
• South Korea
  • Busan, South Korea, 49241
    • Recruiting
    • Pusan National University Hospital
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 08308
    • Recruiting
    • Korea University Guro Hospital
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • ICO Badalona-H.U. Germans Trias i Pujol
• Sweden
  • Gothenburg, Sweden, 411 36
    • Recruiting
    • Sahlgrenska University Hospital
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitätsspital Basel
  • Bern, Switzerland, 3010
    • Withdrawn
    • Inselspital Bern
• Taiwan
  • Taichung, Taiwan, 407
    • Recruiting
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan Uni Hospital
  • Taoyuan District, Taiwan, 333
    • Active, not recruiting
    • Chang Gung Medical Foundation - Linkou
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • Barts & London School of Med
• United States
  • California
    • Duarte, California, United States, 91010
      • Withdrawn
      • City of Hope National Medical Center
    • Huntington Beach, California, United States, 92648
      • Withdrawn
      • City of Hope - Seacliff
    • Irvine, California, United States, 92618
      • Withdrawn
      • City of Hope at Irvine Lennar
    • La Jolla, California, United States, 92093
      • Withdrawn
      • UCSD Moores Cancer Center
    • Long Beach, California, United States, 90813
      • Withdrawn
      • City of Hope - Long Beach Elm
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901-8108
      • Recruiting
      • Florida Cancer Specialists - SOUTH - SCRI - PPDS
    • St. Petersburg, Florida, United States, 33705-1400
      • Recruiting
      • Florida Cancer Specialists - NORTH - SCRI - PPDS
    • West Palm Beach, Florida, United States, 33401-3406
      • Recruiting
      • Florida Cancer Specialists - EAST - SCRI - PPDS
  • New York
    • Mineola, New York, United States, 11501
      • Recruiting
      • NYU Langone Hospital - Long Island
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Cancer Center
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center - Montefiore Medical Park
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Md Anderson Cancer Center
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Recruiting
      • Oncology & Hematology Associates of Southwest Virginia, Inc
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmation of Biomarker eligibility
• Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
• No prior systemic treatment for advanced unresectable or metastatic NSCLC
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment.

Exclusion Criteria:

• Known concomitant second oncogenic driver with available targeted treatment
• Squamous cell histology NSCLC
• Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C)
• Prior treatment with a KRAS G12C inhibitor
• Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment
• History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
• Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
• Co-morbid condition that is an absolute contraindication to treatment with corticosteroids
• Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation.
• Participants with brain metastases for whom complete surgical resections is clinically appropriate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B - Combination Dose Finding + Dose Expansion; Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.	Drug: Pembrolizumab; Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.; Drug: Carboplatin; Participants will receive IV carboplatin Q3W for four 21-day cycles.; Drug: Cisplatin; Participants will receive IV cisplatin Q3W for four 21-day cycles.; Drug: Pemetrexed; Participants will receive IV pemetrexed Q3W.; Drug: Divarasib; Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Experimental: Cohort A - Combination Dose Finding + Dose Expansion; Participants will be enrolled in different cohorts to receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W). During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.	Drug: Pembrolizumab; Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.; Drug: Divarasib; Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Experimental: Cohort C - Dose Expansion; Participants enrolled in this cohort will receive one dose level of divarasib QD.	Drug: Divarasib; Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Experimental: Cohort D - Dose Expansion; Participants enrolled in this cohort will receive one dose level of divarasib QD.	Drug: Divarasib; Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE		Baseline up to approximately 5 years
Objective Response Rate (ORR)	The percentage of participants who experience a complete response or partial response, as determined by the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 5 years
Duration of Response (DOR)	The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1	Approximately 5 years
Progression Free Survival (PFS)	The time from randomization, or date of first treatment for participants enrolled prior to the expansion stage, to the first occurrence of disease progression or death from any cause during the study (whichever occurs first), as determined by the investigator according to RECIST v1.1	Approximately 5 years
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)		Approximately 5 years
Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria		Approximately 5 years
Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE		Approximately 5 years
Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46)		Approximately 5 years
Plasma or CSF Concentration of Divarasib at Specified Timepoints	Optional CSF samples may be collected at the time of disease progression or at any time during the study for participants who have provided written consent and if collection of CSF sample is deemed clinically feasible. Matched optional plasma samples may be drawn at the same time.	Approximately 5 years
Identification of Divarasib Recommended Dose	The recommended dose will be based upon the totality of safety, activity, and PK data.	Approximately 5 years
Central Nervous System (CNS) Response	Defined as the percentage of participants who experience a complete response or partial response in the brain, as determined by the investigator according to modified RECIST	Approximately 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2023
• Primary Completion (Estimated): January 29, 2032
• Study Completion (Estimated): January 29, 2032

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Platinum Compounds; Pemetrexed; Carboplatin; Cisplatin; pembrolizumab
• Other Study ID Numbers: BO44426; 2022-003048-28 (EudraCT Number); 2023-507171-22-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No