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 (Krascendo 1)

April 17, 2026 updated by: Hoffmann-La Roche

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Patients With Previously Treated KRAS G12C-Positive Advanced or Metastatic Non-Small Cell Lung Cancer

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

338

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1280AEB
        • Hospital Britanico
      • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
        • Centro Oncologico Korben
  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • St Leonards, New South Wales, Australia, 2065
        • GenesisCare North Shore
    • Queensland
      • Birtinya, Queensland, Australia, 4575
        • Sunshine Coast University Hospital
    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Lyell McEwin Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter Maccallum Cancer Centre
  • Austria
      • Vienna, Austria, 1210
        • Krankenhaus Nord - Klinik Floridsdorf
  • Belgium
      • Aalst, Belgium, 9300
        • AZORG Campus Aalst-Moorselbaan
      • Brussels, Belgium, 1090
        • UZ Brussel
      • Brussels, Belgium, 1200
        • Cliniques Universitaires St-Luc
      • Edegem, Belgium, 2650
        • UZ Antwerpen
      • Hasselt, Belgium, 3500
        • Jessa Zkh (Campus Virga Jesse)
      • Liège, Belgium, 4000
        • CHU de Liège (Sart Tilman)
      • Mont-godinne, Belgium, 5530
        • CHU UCL Mont-Godinne
      • Roeselare, Belgium, 8800
        • AZ Delta (Campus Rumbeke)
      • Sint-Niklaas, Belgium, 9100
        • Vitaz
      • Wilrijk, Belgium, 2610
        • ZAS Sint Augustinus Wilrijk
  • Brazil
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41253-190
        • Hospital Sao Rafael - HSR
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Hospital de Cancer de Barretos
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Hospital de Base de Sao Jose do Rio Preto
      • São Paulo, São Paulo, Brazil, 01308-050
        • Hospital Sirio-Libanes
      • São Paulo, São Paulo, Brazil, 01323-903
        • Hospital Alemao Oswaldo Cruz
  • Canada
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health Centre - Brampton Civic Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • Denmark
      • Aarhus N, Denmark, 8200
        • Aarhus Universitetshospital
      • Herlev, Denmark, 2730
        • Herlev Hospital
      • Herning, Denmark, 7400
        • Regionshospitalet Gødstrup
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Central Hospital
      • Kuopio, Finland, 70211
        • Kuopio Uni Hospital
  • France
      • Brest, France, 29200
        • CHRU Brest
      • Bron, France, 69677
        • Hôpital Louis Pradel
      • Bron, France, 69500
        • CHU Toulouse
      • Lille, France, 59037
        • CHRU Lille
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Montpellier, France, 34295
        • CHU Montpellier
      • Nice, France, 06100
        • Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
      • Paris, France, 75970
        • Hôpital Tenon
      • Pessac, France, 33604
        • CHU Bordeaux
      • Saint-Quentin, France, 2100
        • CH de Saint Quentin
      • Strasbourg, France, 67091
        • CHRU de Strasbourg
      • Toulon, France, 83041
        • Hia Sainte Anne
  • Germany
      • Berlin, Germany, 13125
        • Evangelische Lungenklinik Berlin
      • Berlin, Germany, 14165
        • Helios Klinikum Emil von Behring GmbH
      • Cologne, Germany, 51109
        • Klinikum Koeln-Merheim
      • Essen, Germany, 45147
        • Universitätsklinikum Essen
      • Essen, Germany, 45136
        • KEM/Evang. Kliniken Essen Mitte gGmbH
      • Esslingen am Neckar, Germany, 73730
        • Klinikum Esslingen
      • Gauting, Germany, 82131
        • Asklepios Fachkliniken GmbH
      • Großhansdorf, Germany, 22927
        • LungenClinic Grosshansdorf GmBH
      • Heidelberg, Germany, 69126
        • Thoraxklinik Heidelberg gGmbH
      • Hemer, Germany, 58675
        • Lungenklinik Hemer
      • Homburg, Germany, 66421
        • Universität des Saarlandes
      • Löwenstein, Germany, 74245
        • SLK Kliniken Heilbronn GmbH, Standort Fachklinik Löwenstein
      • Lübeck, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein
      • München, Germany, 81925
        • Klinikum Bogenhausen
      • Münster, Germany, 48149
        • Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg
      • Würzburg, Germany, 97074
        • Klinikum Würzburg Mitte gGmbH
  • Greece
      • Athens, Greece, 115 27
        • Uoa Sotiria Hospital
      • Athens, Greece, 11526
        • Errikos Dynan Hospital
      • Larissa, Greece, 411 10
        • University Hospital of Larissa
      • Thessaloniki, Greece, 546 39
        • Theageneio Hospital
      • Thessaloniki, Greece, 55236
        • Ag. Loukas Hospital
  • Hong Kong
      • Hong Kong, Hong Kong
        • Tuen Mun Hospital
      • Shatin, Hong Kong
        • Prince of Wales Hosp
  • Italy
    • Apulia
      • Bari, Apulia, Italy, 70124
        • Irccs Ist. Tumori Giovanni Paolo Ii
    • Emilia-Romagna
      • Parma, Emilia-Romagna, Italy, 43100
        • A.O. Universitaria Di Parma
    • Lazio
      • Rome, Lazio, Italy, 00144
        • IRCCS Istituto Regina Elena (IFO)
    • Liguria
      • Genoa, Liguria, Italy, 16132
        • Ospedale Policlinico San Martino
    • Sardinia
      • Sassari, Sardinia, Italy, 07100
        • Ospedale Civile SS Annunziata
    • Tuscany
      • Florence, Tuscany, Italy, 50139
        • Azienda Ospedaliero-Universitaria Careggi
      • Pisa, Tuscany, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana
    • Veneto
      • Padova, Veneto, Italy, 35128
        • IRCCS Istituto Oncologico Veneto (IOV)
  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Miyagi, Japan, 981-0914
        • Sendai Kousei Hospital
      • Osaka, Japan, 589-8511
        • Kindai University Hospital
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR
      • Wakayama, Japan, 641-8510
        • Wakayama Medical University Hospital
  • Mexico
      • Mexico City, Mexico, 06700
        • ARKE Estudios Clínicos S.A. de C.V.
  • Netherlands
      • 's-Hertogenbosch, Netherlands, 5223 GZ
        • Jeroen Bosch ziekenhuis
      • Arnhem, Netherlands, 6815 AD
        • Ziekenhuis Rijnstate
      • Breda, Netherlands, 4818CK
        • Amphia Ziekenhuis
      • Harderwijk, Netherlands, 3844 DG
        • Ziekenhuis St. Jansdal
      • Leidschendam, Netherlands, 2262 BA
        • Medisch Centrum Haaglanden, locatie Antoniushove
      • Zwolle, Netherlands, 8025 AB
        • Isala
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
      • Warsaw, Poland, 01-138
        • Instytut Gruzlicy i Chorob Pluc
      • Wroc?aw, Poland, 53-439
        • Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii
  • Portugal
      • Braga, Portugal, 4710-243
        • Hospital de Braga
      • Coimbra, Portugal, 3000-075
        • CHUC - Unidade de Pneumologia Oncológica
      • Lisbon, Portugal, 1400-038
        • Centro Clinico Champalimaud
      • Porto, Portugal, 4200-072
        • IPO do Porto
      • Porto, Portugal, 4099-001
        • Centro Hospitalar do Porto ? Hospital de Santo António
  • Singapore
      • Singapore, Singapore, 168583
        • National Cancer Centre
  • South Korea
      • Gyeonggi-do, South Korea, 16247
        • St. Vincent's Hospital
      • Incheon, South Korea, 21565
        • Gachon University Gil Medical Center
      • Jeollanam-do, South Korea, 58128
        • Chonnam National University Hwasun Hospital
      • Seongnam-si, South Korea, 463-707
        • Seoul National University Bundang Hospital
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Vall Hebron
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Málaga, Spain, 29010
        • Hospital Regional Universitario de Málaga
      • Valencia, Spain, 46026
        • Hospital Universitario la Fe
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Institut Catala d Oncologia Hospitalet
    • Sevilla
      • Seville, Sevilla, Spain, 41014
        • Hospital Nuestra Señora de Valme
  • Sweden
      • Gävle, Sweden, 80187
        • Gavle Sjukhus
  • Taiwan
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 00100
        • National Taiwan University Hospital
      • Taoyuan District, Taiwan, 333
        • Chang Gung Medical Foundation - Linkou
  • Thailand
      • Bangkok, Thailand, 10300
        • Vajira Hospital
      • Bangkok, Thailand, 10700
        • Siriraj Hospital - Chulabhorn Bone Marrow Transplant Centre
      • Songkhla, Thailand, 90110
        • Songklanagarind Hospital
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital
      • Cottingham, United Kingdom, HU16 5JQ
        • Castle Hill Hospital
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre
      • Leeds, United Kingdom, LS9 7TF
        • St James University Hospital
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital - London
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital - Cancer Centre
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham City Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital (Sutton)
      • Torquay, United Kingdom, TQ27AA
        • Torbay Hospital
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner Health MD Anderson AZ
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology / Oncology Clinic
      • Los Angeles, California, United States, 90017-4803
        • Los Angeles Cancer Network
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale Cancer Center
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
      • St. Petersburg, Florida, United States, 33701-4553
        • Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg)
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Maine
      • Westbrook, Maine, United States, 04092
        • New England Cancer Specialists
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0934
        • University of Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Cancer and Hematology Centers of Western Michigan
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Minnesota Oncology Edina
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Ohio
      • Maumee, Ohio, United States, 43537
        • Taylor Cancer Research Center
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Oncology Associates of Oregon, P.C
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny Cancer Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC - Chattanooga
      • Memphis, Tennessee, United States, 38120
        • Baptist Clinical Research Institute
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • Fort Worth, Texas, United States, 76104
        • JPS Health Network
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • Longview, Texas, United States, 75601
        • Texas Oncology - Northeast Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Divarasib
Participants will receive divarasib orally, once daily (QD).
Drug: Divarasib
Divarasib will be administered orally QD
Active Comparator: KRAS G12C inhibitor
Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
Drug: Sotorasib
Sotorasib will be administered orally QD
Drug: Adagrasib
Adagrasib will be administred orally BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 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)
Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to approximately 4 years
OS is defined as the time from randomization to death from any cause
Up to approximately 4 years
Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale
Time Frame: Baseline up to approximately 4 years
Baseline up to approximately 4 years
TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale
Time Frame: Baseline up to approximately 4 years
Baseline up to approximately 4 years
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 4 years
Up to approximately 4 years
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time Frame: Up to approximately 4 years
Up to approximately 4 years
Change from Baseline in Diarrhea, Nausea, Vomiting, Anorexia, Alopecia, Dyspnea, Cough, Constipation, Myalgia, Headache, and Rash/Acne as Assessed Through use of the NCI PRO-CTCAE
Time Frame: Baseline up to approximately 4 years
Baseline up to approximately 4 years
Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46)
Time Frame: Up to approximately 4 years
Up to approximately 4 years
Change from Baseline in Cough, Chest Pain, Dyspnea, Physical and Role Functioning, and Global Health Status score/Quality of Life Score (GHS/QoL) at Each Timepoint as Assessed Through use of the EORTC QLQ-LC13 and QLQ-C30
Time Frame: Baseline up to approximately 4 years
Baseline up to approximately 4 years
TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales
Time Frame: Up to approximately 4 years
Up to approximately 4 years
TTCD on the Chest Pain Scale of the QLQ-LC13 Scales
Time Frame: Up to approximately 4 years
Up to approximately 4 years
Confirmed Objective Response
Time Frame: Up to approximately 4 years
Confirmed objective response is defined as complete response (CR) or partial response (PR) on two occasions ≥ 4 weeks apart, as determined by BICR according to RECIST v1.1
Up to approximately 4 years
Duration of Response (DOR)
Time Frame: Up to approximately 4 years
DOR is defined as the time from the first occurrence of a documented confirmed objective response to disease progression, as determined by BICR according to RECIST v1.1, or death from any cause (whichever occurs first)
Up to approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

Chugai Pharmaceutical

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2024

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

November 30, 2029

Study Registration Dates

First Submitted

July 5, 2024

First Submitted That Met QC Criteria

July 5, 2024

First Posted (Actual)

July 11, 2024

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

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BO45217
  • 2024-510908-37-00 (Other Identifier: 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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