Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Sponsor: Novartis Pharmaceuticals
ClinicalTrials ID:NCT05358249
This Phase Ib/II study evaluates JDQ443 with select therapies in advanced KRAS G12C mutant tumors. Eligible patients include those with advanced solid tumors post-standard therapy. Interventions include JDQ443 (KRAS G12C inhibitor), trametinib (MEK inhibitor), ribociclib (CDK4/6 inhibitor), and cetuximab (EGFR inhibitor). Treatment arms may advance to Phase II based on safety and dose findings.
Patient Parameters
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Program Overview
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.
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.
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
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Massachusetts General Hospital | 02114 | Boston | Massachusetts |
| Dana Farber Cancer Institute | 02215 | Boston | Massachusetts |
| NYU School of Medicine | 10015 | New York | New York |
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