Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (KontRASt-03)

Novartis

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Colorectal Carcinoma; Non-Small Cell Lung Carcinoma; Nonsmall Cell Lung Cancer; Carcinoma, Non-Small Cell Lung; KRAS G12C Mutant Solid Tumors; Colorectal Tumors; Carcinoma, Non-Small-Cell Lung; Neoplasms, Colorectal; Colorectal Neoplasms; Colorectal Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: trametinib; Biological: cetuximab; Drug: JDQ443; Drug: Ribociclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05358249

CJDQ443E12101

2021-006196-42 (EudraCT Number)

Details and patient eligibility

About

This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.

Full description

JDQ443 will be considered "backbone" treatment in this trial and combined with selected therapies, or "partner(s)". The combination of a backbone and a partner will constitute a treatment arm. After dose escalation, treatment arms that reach a maximum tolerated dose /recommended dose and are determined to be safe may, but are not required to, proceed to Phase II to further explore safety, tolerability, and anti-tumor activity.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Dose Escalation:

• Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.

Phase II:

• Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
• Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.

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 treating institution's guidelines.

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 a subset of groups in Phase II.
• Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease
• Clinically significant cardiac disease or risk factors at screening
• Insufficient bone marrow, hepatic or renal function at screening Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 3 patient groups

JDQ443+trametinib

Experimental group

Description:

JDQ443 in combination with trametinib

Treatment:

Drug: JDQ443

Drug: trametinib

JDQ443+ribociclib

Experimental group

Description:

JDQ443 in combination with ribociclib

Treatment:

Drug: Ribociclib

Drug: JDQ443

JDQ443+cetuximab

Experimental group

Description:

JDQ443 in combination with cetuximab

Treatment:

Drug: JDQ443

Biological: cetuximab