Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

NCT05358249 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CJDQ443E121012021-006196-42
• Study Type: interventional
• Target: 74
• Locations: 8 countries
• Sites: 13

Brief Summary

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.

Conditions

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

Keywords

KRAS G12C; targeted therapy; NSCLC; CRC; advanced solid tumors; JDQ443; trametinib; ribociclib; cetuximab

Outcome Measures

Primary Outcomes (5)

• Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.

  28 days

• Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment

  All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).

  24 months

• Dose escalation: Frequency of dose interruptions and reductions, by treatment

  The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.

  24 months

• Dose Escalation: Dose intensity by treatment

  Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.

  24 months

• PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1

  ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).

  24 months

Secondary Outcomes (16)

• Dose escalation and Phase II: ORR by local review per RECIST 1.1

  24 months

• Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1

  24 months

• Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1

  24 months

• Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1

  24 months

• Phase II: DCR by BIRC per RECIST 1.1

  24 months

Study Arms (3)

JDQ443+trametinib

EXPERIMENTAL

JDQ443 in combination with trametinib

Drug: JDQ443; Drug: trametinib

JDQ443+ribociclib

EXPERIMENTAL

JDQ443 in combination with ribociclib

Drug: JDQ443; Drug: Ribociclib

JDQ443+cetuximab

EXPERIMENTAL

JDQ443 in combination with cetuximab

Drug: JDQ443; Biological: cetuximab

Interventions

JDQ443 DRUG

KRAS G12C inhibitor, oral

JDQ443+cetuximab; JDQ443+ribociclib; JDQ443+trametinib

trametinib DRUG

MEK inhibitor, oral

Also known as: TMT212

JDQ443+trametinib

Ribociclib DRUG

CDK4/6 inhibitor, oral

Also known as: LEE011

JDQ443+ribociclib

cetuximab BIOLOGICAL

EGFR inhibitor, intravenous

JDQ443+cetuximab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

NYU School of Medicine

New York, New York, 10015, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

JDQ443; trametinib; ribociclib; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: October 24, 2022
• Primary Completion (Estimated): July 29, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); KR (1); SG (1); ES (3); US (3); DE (1); FR (2); IT (1)