Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (KontRASt-01)

Novartis

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

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

Treatments: Drug: TNO155; Drug: JDQ443; Biological: tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04699188

2020-004129-22 (EudraCT Number)

CJDQ443A12101

Details and patient eligibility

About

This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.

Enrollment: 344 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies
• ECOG Performance Status of 0 or 1
• At least one measurable lesion as defined by RECIST 1.1
• Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion

Exclusion criteria

• Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
• Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible
• Clinically significant cardiac disease or risk factors at screening
• A medical condition that results in increased photosensitivity 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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344 participants in 4 patient groups

Arm A

Experimental group

Description:

JDQ443

Treatment:

Drug: JDQ443

Arm B

Experimental group

Description:

JDQ443 in combination with TNO155

Treatment:

Drug: JDQ443

Drug: TNO155

Arm C

Experimental group

Description:

JDQ443 in combination with tislelizumab

Treatment:

Biological: tislelizumab

Drug: JDQ443

Arm D

Experimental group

Description:

JDQ443 in combination with TNO155 and tislelizumab

Treatment:

Biological: tislelizumab

Drug: JDQ443

Drug: TNO155