Last Update: Feb 09, 2024
KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
ClinicalTrials.gov Identifier:
Novartis Reference Number:CJDQ443E12101
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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.

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.

KRAS G12C Mutant Solid Tumors, Carcinoma, Non-Small Cell Lung, Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Nonsmall Cell Lung Cancer, Colorectal Cancer, Colorectal Carcinoma, Colorectal Neoplasms, Colorectal Tumors, Neoplasms, Colorectal
Phase 1, Phase 2
Recruiting
346
Oct 24, 2022
Jun 16, 2027
All
18 Years - (Adult, Older Adult)

Interventions

Biological

cetuximab

EGFR inhibitor, intravenous
Drug

JDQ443

KRAS G12C inhibitor, oral
Drug

Ribociclib

CDK4/6 inhibitor, oral
Drug

trametinib

MEK inhibitor, oral

Eligibility Criteria

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

Study Location

Novartis Investigative Site

Recruiting

Leuven,3000,Belgium

Novartis Investigative Site

Recruiting

Lyon,69373,France

Novartis Investigative Site

Recruiting

Bordeaux,33076,France

Novartis Investigative Site

Recruiting

Freiburg,79106,Germany

Novartis Investigative Site

Recruiting

Ulm,89081,Germany

Novartis Investigative Site

Recruiting

Milano,MI,20162,Italy

Novartis Investigative Site

Recruiting

Seoul,03080,Korea, Republic of

Novartis Investigative Site

Recruiting

Singapore,168583,Singapore

Novartis Investigative Site

Recruiting

Madrid,28034,Spain

Novartis Investigative Site

Recruiting

Madrid,28050,Spain

Novartis Investigative Site

Recruiting

Barcelona,Catalunya,08036,Spain

Dana Farber Cancer Institute Dept.of DFCI

Recruiting

Boston,Brian Schwalm email: [email protected] -- Jia Luo,02215 - Massachusetts,United States

NYU School of Medicine Langone Health

Recruiting

New York,Sasha Richardson (212-731-5662) email: [email protected] -- Janice Mehnert,10015 - New York,United States

Massachusetts General Hospital .

Recruiting

Boston,Aaron Paul Doss email: [email protected] -- Rebecca Heist,02114 - Massachusetts,United States

Worldwide Contacts

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Novartis Pharmaceuticals

Novartis Pharmaceuticals