study of JDQ443 in advanced cancer with a specific mutation (G12C) of the KRAS gene

Phase 1

• Conditions: advanced solid tumors harboring the KRAS G12C mutation; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); 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: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 25.1Level: LLTClassification code 10069759Term: KRAS mutationSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004129-22-BE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-12
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 475

Inclusion Criteria

Dose Escalation:
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are intolerant or ineligible to approved therapies.
Dose Expansion:
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received a platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy. Treatment with a prior KRAS G12C inhibitor is not allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received a platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy, and one treatment line of a direct KRAS G12C inhibitor given as a single agent and discontinued within 6 months of the first day of study treatment.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant NSCLC who have received a platinum-based chemotherapy regimen and an immune checkpoint inhibitor therapy either in combination or in sequence, unless patient was ineligible to receive such therapy. The patient must have at least one untreated brain metastasis. Treatment with a prior KRAS G12C inhibitor is not allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received standard-of-care therapy, including a fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy. Treatment with a prior KRAS G12C inhibitor is not allowed.
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors other than NSCLC or CRC who have received standard of care therapy or are intolerant or ineligible to approved
therapies. Treatment with a prior KRAS G12C inhibitor is not allowed.
All Patients:
• ECOG performance status of 0 or 1.
• Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the institution’s own guidelines and requirements for such procedures.
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 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 190

Exclusion Criteria

• Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations.
• Prior treatment with a KRAS G12C inhibitor is excluded for patients in the single agent dose escalation arm and a subset of groups in dose expansion.
• Prior treatment with a SHP2 or SOS1 inhibitor is not allowed for NSCLC patients enrolled into the dose expansion parts of the JDQ443 single agent and JDQ443 plus TNO155 expansion arms.
• Untreated brain metastases, (applicable to all patients except the brain metastasis group), symptomatic brain metastases (applicable to all
patients), or known leptomeningeal disease (applicable to all patients)
• Clinically significant cardiac disease or risk factors at screening
• Insufficient bone marrow, hepatic or renal function at screening

Study & Design

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