A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination with Other Anti-Cancer Therapies in Patients with Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer with a KRAS G12C Mutatio

Phase 1

Active, not recruiting

• Conditions: ntreated Advanced or Metastatic Non-Small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-003048-28-PL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-29
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

- Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- No prior systemic treatment for advanced unresectable or metastatic NSCLC
-Confirmation of Biomarker eligibility:
.. Documented history of the KRAS G12C mutation
.. Documented history of PD-L1 expression
- For Cohort A, PD-L1 tumor cell expression >= 1% is required to
be eligible
- For Cohort B, PD-L1 tumor cell expression is not required to be
eligible
- Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

- Known concomitant second oncogenic driver with available targeted treatment
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Prior treatment with a KRAS G12C inhibitor
- Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin,
or cisplatin (Cohort B only)
- History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
- Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified