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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05358249
Other study ID # CJDQ443E12101
Secondary ID 2021-006196-42
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date October 24, 2022
Est. completion date June 16, 2027

Study information

Verified date February 2024
Source Novartis
Contact Novartis Pharmaceuticals
Phone 1-888-669-6682
Email novartis.email@novartis.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 346
Est. completion date June 16, 2027
Est. primary completion date May 5, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
JDQ443
KRAS G12C inhibitor, oral
trametinib
MEK inhibitor, oral
Ribociclib
CDK4/6 inhibitor, oral
Biological:
cetuximab
EGFR inhibitor, intravenous

Locations

Country Name City State
Belgium Novartis Investigative Site Leuven
France Novartis Investigative Site Bordeaux
France Novartis Investigative Site Lyon
Germany Novartis Investigative Site Freiburg
Germany Novartis Investigative Site Ulm
Italy Novartis Investigative Site Milano MI
Korea, Republic of Novartis Investigative Site Seoul
Singapore Novartis Investigative Site Singapore
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Madrid
United States Dana Farber Cancer Institute Dept.of DFCI Boston Massachusetts
United States Massachusetts General Hospital . Boston Massachusetts
United States NYU School of Medicine Langone Health New York New York

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Singapore,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 Dose escalation and Phase II: ORR by local review per RECIST 1.1 ORR is the proportion of patients with a BOR of CR or PR. 24 months
Secondary Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1 DCR is the proportion of patients with a BOR of CR or PR or Stable Disease (SD). The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth. 24 months
Secondary Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1 Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. 24 months
Secondary Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1 PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. 24 months
Secondary Phase II: DCR by BIRC per RECIST 1.1 DCR is the proportion of patients with a BOR of CR or PR or SD. The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth. 24 months
Secondary Phase II: DoR by BIRC per RECIST 1.1 Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. 24 months
Secondary Phase II: PFS by BIRC per RECIST 1.1 PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. 24 months
Secondary Phase II: Overall survival (OS) OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. 24 months
Secondary Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) 5 months
Secondary Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm Observed concentration at the end of a dosing interval (taken directly before next administration) 5 months
Secondary Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) 5 months
Secondary Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1) 5 months
Secondary Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm The AUC from time zero to infinity (mass x time x volume-1) 5 months
Secondary Phase II: 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
Secondary Phase II: 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
Secondary Phase II: Dose intensity by treatment Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response. 24 months
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