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NCT Number: 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

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).

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This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Britanico, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Divarasib

Drug

Divarasib will be administered orally QD

Sotorasib

Drug

Sotorasib will be administered orally QD

Adagrasib

Drug

Adagrasib will be administred orally BID

Primary outcomes

  1. 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)

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: Up to approximately 4 years

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

  2. 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

  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

    Time frame: Baseline up to approximately 4 years

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

    Time frame: Baseline up to approximately 4 years

  5. 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)

  6. Percentage of Participants with Adverse Events (AEs)

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: Baseline up to approximately 4 years

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

    Time frame: Up to approximately 4 years

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

    Time frame: Up to approximately 4 years

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • Chugai Pharmaceutical

Registry information

Official study 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

Acronym: Krascendo 1

Important dates

Study start
2024
Primary completion
2026
Study completion
2029
First posted
Jul 11, 2024
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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