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Phase III: Divarasib in Metastatic NSCLC (KRASCENDO 1)

Clinical Trial Overview

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 (NSCLC)

Objective

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)

Trial Design

2L= second-line; 3L= third-line; 4L= fourth line; NSCLC= non-small cell lung cancer; ECOG= Eastern Cooperative Oncology Group; RECIST v1.1= Response Evaluation Criteria in Solid Tumors version 1.1.

Primary Endpoints

Progression-Free Survival (PFS)

Secondary Endpoints

Overall Survival (OS)
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
TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale
Percentage of Participants with Objective Response Duration of Response (DOR)
Percentage of Participants with Adverse Events (AEs)
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)
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
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)
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
TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales
TTCD on the Chest Pain Scale of the QLQ-LC13 Scales

AEs= Adverse Events; DOR= Duration of Response; EORTC QLQ-C30= European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ-13= Quality-of-Life Questionnaire-Supplemental Lung Cancer Module; GHS/QoL= Global Health Status score/Quality of Life Score; OS= Overall Survival; PFS= Progression-Free Survival; PRO-CTCAE= Patient-Reported Outcomes Common Terminology Criteria for Adverse Events; TTCD= Time to Confirmed Deterioration.

Divarasib

Other names: GDC-6036
Modality: Kirsten rat sarcoma virus gene (KRAS) G12C inhibitor

QUICK LINKS

Clinical Trial Overview

Inclusion and Exclusion Criteria

Enrollment and Resources

View on ClinicalTrials.gov

Inclusion and Exclusion Criteria

Key Inclusion Criteria

Key Exclusion Criteria

Unequivocal histologically or cytologically confirmed diagnosis of unresectable Stage IIIc, per the American Joint Committee on Cancer Staging System (AJCC) (Amin et al. 2017) not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
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 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

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

AJCC= american joint committee on cancer staging system; CNS= central nervous system; ECOG= eastern cooperative pncology group; FFPE= formalin-fixed, paraffin-embedded; OS= overall survival; RECIST= response evaluation criteria in solid tumors;

Enrollment & Resources

Enrollment

For more information on eligibility criteria, view the study or reach out to our team.

Web

ClinicalTrials.gov
Identifier: NCT06497556

Phone

1-888-662-6728
(US and Canada)

Email

[email protected]

Clinical Trial Site Locations

Clinical Trial Site Locations

For more information on recruitment status, or where the study is being conducted

Visit ClinicalTrials.gov

Information is consistent with ClinicalTrials.gov as of April 17, 2025. Products under investigation have not been approved for use outside of the clinical trial setting. This information is presented only for the purposes of providing an overview of clinical trials and should not be construed as a recommendation for use of any product for unapproved purposes.

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