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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

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 (Krascendo1)

Venice Archer

F. Hoffmann-La Roche Ltd.

1-1 NIHONBASHI-MUROMACHI 2-CHOME, CHUO-KU,Tokyo

clinical-trials@chugai-pharm.co.jp

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 NIHONBASHI-MUROMACHI 2-CHOME, CHUO-KU,Tokyo

+81-120189706

clinical-trials@chugai-pharm.co.jp

Not Recruiting

Oct. 31, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
2. 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.
Prior systemic treatment must include a platinum-based doublet chemotherapy regimen and a PD-L1/PD-1 inhibitor, either given in combination as one line of therapy or as individual lines of therapy.
3. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Documentation of the presence of a KRAS G12C mutation
5. 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
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Life expectancy of >= 12 weeks

1. Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
2. Malabsorption syndrome or other condition that would interfere with enteral absorption
3. Known concomitant second oncogenic driver
4. Mixed small-cell lung cancer or large cell neuroendocrine histology
5. Known and untreated, or active central nervous system (CNS) metastases
6. Leptomeningeal disease or carcinomatous meningitis
7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
8. 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
9. Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
10. More than 30 Gy of radiotherapy to the lung within 6 months of randomization
11. Uncontrolled tumor-related pain
12. Unresolved toxicities from prior anticancer therapy
13. 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

Both

2L+ NSCLC with KRAS G12C positive

Divarasib: Divarasib will be administered orally QD
Sotorasib: Sotorasib will be administered orally QD

efficacy
1. Progression-Free Survival (PFS)

safety, efficacy,
2. Overall Survival (OS)
3. Time to Confirmed Deterioration (TTCD) on the EORTC QLQ-C30 Dyspnea Item and Physical Functioning Scale
4. TTCD on the QLQ-LC13 Cough Scale
5. Percentage of Participants with Objective Response Rate (ORR)
6. Duration of Response (DOR)
7. Percentage of Participants with Adverse Events (AEs)
8. Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI PRO-CTCAE
9. 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
10. 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)
11. 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 QLQC30
12. TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales
13. TTCD on the Chest Pain Scale of the QLQ-LC13 Scales

+81-86-235-7534

Aug. 21, 2024

Yes

Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

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