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AzTrials

Non-Small Cell Lung CancerPhase 3Krascendo 1NCT06497556

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

A Phase 3 study testing Divarasib, Sotorasib and Adagrasib in people with Non-Small Cell Lung Cancer and KRAS G12C Lung Cancer, run by Hoffmann-La Roche at 151 sites in 26 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Divarasib, Sotorasib and Adagrasib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
338 participants
Where
151 sitesin 26 countries
Study dates
23 Sep 2024to 30 Nov 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

151 sites in 26 countries.

151 sites in 26 countries

United States25 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109-0934

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Tennessee Oncology, PLLC - Chattanooga

    Chattanooga, Tennessee, 37404

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Minnesota Oncology Edina

    Edina, Minnesota, 55435

  • Oncology Associates of Oregon, P.C

    Eugene, Oregon, 97401

  • JPS Health Network

    Fort Worth, Texas, 76104

  • Banner Health MD Anderson AZ

    Gilbert, Arizona, 85234

  • Cancer and Hematology Centers of Western Michigan

    Grand Rapids, Michigan, 49503

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Texas Oncology - Northeast Texas

    Longview, Texas, 75601

  • Los Angeles Cancer Network

    Los Angeles, California, 90017-4803

  • UCLA Hematology / Oncology Clinic

    Los Angeles, California, 90095

  • Taylor Cancer Research Center

    Maumee, Ohio, 43537

  • Baptist Clinical Research Institute

    Memphis, Tennessee, 38120

  • University of Miami

    Miami, Florida, 33136

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Yale Cancer Center

    New Haven, Connecticut, 06519

  • Columbia University Medical Center

    New York, New York, 10032

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Allegheny Cancer Center

    Pittsburgh, Pennsylvania, 15212

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of California, San Francisco

    San Francisco, California, 94158

  • Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg)

    St. Petersburg, Florida, 33701-4553

  • New England Cancer Specialists

    Westbrook, Maine, 04092

Other trials in United States

Germany17 sites

  • Evangelische Lungenklinik Berlin

    Berlin, 13125

  • Helios Klinikum Emil von Behring GmbH

    Berlin, 14165

  • Klinikum Koeln-Merheim

    Cologne, 51109

  • KEM/Evang. Kliniken Essen Mitte gGmbH

    Essen, 45136

  • Universitätsklinikum Essen

    Essen, 45147

  • Klinikum Esslingen

    Esslingen am Neckar, 73730

  • Asklepios Fachkliniken GmbH

    Gauting, 82131

  • LungenClinic Großhansdorf GmbH

    Großhansdorf, 22927

  • Thoraxklinik Heidelberg gGmbH

    Heidelberg, 69126

  • Lungenklinik Hemer

    Hemer, 58675

  • Universität Des Saarlandes

    Homburg, 66421

  • SLK Kliniken Heilbronn GmbH, Standort Fachklinik Löwenstein

    Löwenstein, 74245

  • Universitätsklinikum Schleswig-Holstein

    Lübeck, 23538

  • Klinikum Bogenhausen

    München, 81925

  • Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie

    Münster, 48149

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Klinikum Würzburg Mitte gGmbH

    Würzburg, 97074

Other trials in Germany

France12 sites

  • CHRU Brest

    Brest, 29200

  • Chu Toulouse

    Bron, 69500

  • Hopital Louis Pradel

    Bron, 69677

  • CHRU Lille

    Lille, 59037

  • Centre Leon Berard

    Lyon, 69373

  • CHU Montpellier

    Montpellier, 34295

  • Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer

    Nice, 06100

  • Hopital Tenon

    Paris, 75970

  • CHU Bordeaux

    Pessac, 33604

  • CH de Saint Quentin

    Saint-Quentin, 2100

  • Chru de Strasbourg

    Strasbourg, 67091

  • Hia Sainte Anne

    Toulon, 83041

Other trials in France

Belgium10 sites

  • AZORG Campus Aalst-Moorselbaan

    Aalst, 9300

  • UZ Brussel

    Brussels, 1090

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • UZ Antwerpen

    Edegem, 2650

  • Jessa Zkh (Campus Virga Jesse)

    Hasselt, 3500

  • CHU de Liège (Sart Tilman)

    Liège, 4000

  • CHU UCL Mont-Godinne

    Mont-godinne, 5530

  • AZ Delta (Campus Rumbeke)

    Roeselare, 8800

  • Vitaz

    Sint-Niklaas, 9100

  • ZAS Sint Augustinus Wilrijk

    Wilrijk, 2610

Other trials in Belgium

United Kingdom9 sites

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Castle Hill Hospital

    Cottingham, HU16 5JQ

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • St James University Hospital

    Leeds, LS9 7TF

  • Guy's Hospital - Cancer Centre

    London, SE1 9RT

  • Royal Marsden Hospital - London

    London, SW3 6JJ

  • Nottingham City Hospital

    Nottingham, NG5 1PB

  • Royal Marsden Hospital (Sutton)

    Sutton, SM2 5PT

  • Torbay Hospital

    Torquay, TQ27AA

Other trials in United Kingdom

Italy8 sites

  • Irccs Ist. Tumori Giovanni Paolo Ii

    Bari, Apulia, 70124

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, Tuscany, 50139

  • Ospedale Policlinico San Martino

    Genoa, Liguria, 16132

  • IRCCS Istituto Oncologico Veneto (IOV)

    Padova, Veneto, 35128

  • A.O. Universitaria Di Parma

    Parma, Emilia-Romagna, 43100

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, Tuscany, 56126

  • IRCCS Istituto Regina Elena (IFO)

    Rome, Lazio, 00144

  • Ospedale Civile SS Annunziata

    Sassari, Sardinia, 07100

Other trials in Italy

Spain8 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08025

  • Hospital Vall Hebron

    Barcelona

  • Institut Catala d Oncologia Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Nuestra Senora de Valme

    Seville, Sevilla, 41014

  • Hospital Universitario la Fe

    Valencia, 46026

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Japan6 sites

  • Kyushu University Hospital

    Fukuoka, 812-8582

  • Sendai Kousei Hospital

    Miyagi, 981-0914

  • Kindai University Hospital

    Osaka, 590-0197

  • National Cancer Center Hospital

    Tokyo, 104-0045

  • The Cancer Institute Hospital of JFCR

    Tokyo, 135-8550

  • Wakayama Medical University Hospital

    Wakayama, 641-8510

Other trials in Japan

Netherlands6 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5223 GZ

  • Ziekenhuis Rijnstate

    Arnhem, 6815 AD

  • Amphia Ziekenhuis

    Breda, 4818CK

  • Ziekenhuis St. Jansdal

    Harderwijk, 3844 DG

  • Medisch Centrum Haaglanden, locatie Antoniushove

    Leidschendam, 2262 BA

  • Isala

    Zwolle, 8025 AB

Other trials in Netherlands

South Korea6 sites

  • St. Vincent's Hospital

    Gyeonggi-do, 16247

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Chonnam National University Hwasun Hospital

    Jeollanam-do, 58128

  • Seoul National University Bundang Hospital

    Seongnam-si, 463-707

  • Seoul National University Hospital

    Seoul, 03080

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Australia5 sites

  • Sunshine Coast University Hospital

    Birtinya, Queensland, 4575

  • Lyell McEwin Hospital

    Elizabeth Vale, South Australia, 5112

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, 3000

  • GenesisCare North Shore

    St Leonards, New South Wales, 2065

Other trials in Australia

Brazil5 sites

  • Hospital de Cancer de Barretos

    Barretos, São Paulo, 14784-400

  • Hospital Sao Rafael - HSR

    Salvador, Estado de Bahia, 41253-190

  • Hospital de Base de Sao Jose do Rio Preto

    São José do Rio Preto, São Paulo, 15090-000

  • Hospital Sírio-Libanês

    São Paulo, São Paulo, 01308-050

  • Hospital Alemao Oswaldo Cruz

    São Paulo, São Paulo, 01323-903

Other trials in Brazil

Greece5 sites

  • Uoa Sotiria Hospital

    Athens, 115 27

  • Errikos Dynan Hospital

    Athens, 11526

  • University Hospital of Larissa

    Larissa, 411 10

  • Theageneio Hospital

    Thessaloniki, 546 39

  • Ag. Loukas Hospital

    Thessaloniki, 55236

Other trials in Greece

Portugal5 sites

  • Hospital de Braga

    Braga, 4710-243

  • CHUC - Unidade de Pneumologia Oncológica

    Coimbra, 3000-075

  • Centro Clinico Champalimaud

    Lisbon, 1400-038

  • Centro Hospitalar do Porto ? Hospital de Santo António

    Porto, 4099-001

  • IPO do Porto

    Porto, 4200-072

Other trials in Portugal

Denmark3 sites

  • Aarhus Universitetshospital

    Aarhus N, 8200

  • Herlev Hospital

    Herlev, 2730

  • Regionshospitalet Gødstrup

    Herning, 7400

Other trials in Denmark

Poland3 sites

  • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

    Gdansk, 80-214

  • Instytut Gruzlicy I Chorob Pluc

    Warsaw, 01-138

  • Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii

    Wroc?aw, 53-439

Other trials in Poland

Taiwan3 sites

  • National Taiwan University Hospital

    Taipei, 00100

  • Taipei Veterans General Hospital

    Taipei, 112

  • Chang Gung Medical Foundation - Linkou

    Taoyuan, 333

Other trials in Taiwan

Thailand3 sites

  • Vajira Hospital

    Bangkok, 10300

  • Siriraj Hospital

    Bangkok, 10700

  • Songklanagarind Hospital

    Songkhla, 90110

Other trials in Thailand

Argentina2 sites

  • Hospital Britanico

    Buenos Aires, C1280AEB

  • Centro Oncologico Korben

    Ciudad Autonoma Buenos Aires, C1426AGE

Other trials in Argentina

Canada2 sites

  • William Osler Health Centre - Brampton Civic Hospital

    Brampton, Ontario, L6R 3J7

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

Finland2 sites

  • Helsinki University Central Hospital

    Helsinki, 00029

  • Kuopio Uni Hospital

    Kuopio, 70211

Other trials in Finland

Hong Kong2 sites

  • Tuen Mun Hospital

    Hong Kong

  • Prince of Wales Hosp

    Shatin

Other trials in Hong Kong

Austria1 site

  • Krankenhaus Nord - Klinik Floridsdorf

    Vienna, 1210

Other trials in Austria

Mexico1 site

  • ARKE Estudios Clínicos S.A. de C.V.

    Mexico City, 06700

Other trials in Mexico

Singapore1 site

  • National Cancer Centre

    Singapore, 168583

Other trials in Singapore

Sweden1 site

  • Gävle Sjukhus

    Gävle, 80187

Other trials in Sweden

About this study

Official title: 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).

Being tested
Divarasib, Sotorasib, Adagrasib
Keywords
Advanced Non-Small Cell Lung Cancer, KRAS G12 Lung Cancer, Advanced Lung Cancer, Metastatic lung cancer, Divarasib, KRAS G12C Inhibitor, KRAS G12C Positive, KRAS Mutation, KRAS G12C Mutation, Lung Cancer Mutation
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DivarasibDrug

    Divarasib will be administered orally QD

  • SotorasibDrug

    Sotorasib will be administered orally QD

  • AdagrasibDrug

    Adagrasib will be administred orally BID

Study groups in NCT06497556
Study groupRoleWhat they receive
DivarasibExperimentalParticipants will receive divarasib orally, once daily (QD).
Receives: Drug: Divarasib
KRAS G12C inhibitorActive comparatorParticipants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
Receives: Drug: Sotorasib; Drug: Adagrasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    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)

    Measured: Up to approximately 4 years

Secondary outcomes (12)

  1. Overall Survival (OS)

    OS is defined as the time from randomization to death from any cause

    Measured: Up to approximately 4 years

  2. Confirmed Objective Response

    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

    Measured: Up to approximately 4 years

  3. 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

    Measured: Baseline up to approximately 4 years

  4. TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale

    Measured: Baseline up to approximately 4 years

  5. Duration of Response (DOR)

    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)

    Measured: Up to approximately 4 years

  6. Percentage of Participants with Adverse Events (AEs)

    Measured: Up to approximately 4 years

  7. 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)

    Measured: Up to approximately 4 years

  8. 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

    Measured: Baseline up to approximately 4 years

  9. 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)

    Measured: Up to approximately 4 years

  10. 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

    Measured: Baseline up to approximately 4 years

  11. TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales

    Measured: Up to approximately 4 years

  12. TTCD on the Chest Pain Scale of the QLQ-LC13 Scales

    Measured: Up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2024
  2. Study start23 Sep 2024
  3. Primary completion19 May 2026
  4. Study completion30 Nov 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
338 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06497556
Sponsor's protocol ID
BO45217
Other IDs
2024-510908-37-00
Acronym
Krascendo 1
Status last verified
Sep 2026
First submitted
5 Jul 2024
Last updated
16 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Skoulidis F, Ahn MJ, Gadgeel S, Popat S, Reinmuth N, van Veggel B, Bozorgmehr F, Bray VJ, Duruisseaux M, Iams WT, Mazieres J, Bonanno L, Decoster L, Niu J, Pantarotto M, Teixeira CHA, Uzun S, Wang B, Chan BA, Felip E, Li MSC, Akamatsu H, Cuppens K, Kim TM, Reck M, Hu Y, Shagan SM, Lin MT, Osaghae U, Hoang T, Wu F, Meng R, Mathisen MS, Solomon BJ. Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C-Mutated NSCLC. N Engl J Med. 2026 Oct 25. doi: 10.1056/NEJMoa2605703. Online ahead of print.

    PubMed 42929675

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Divarasib, Sotorasib and Adagrasib in people with Non-Small Cell Lung Cancer and KRAS G12C Lung Cancer, run by Hoffmann-La Roche at 151 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 151 sites in United States, Germany, France, Belgium, United Kingdom and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Up to approximately 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06497556, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.

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