Clinical trial NCT05358249: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: KRAS G12C
targeted therapy
NSCLC
CRC
advanced solid tumors
JDQ443
trametinib
ribociclib
cetuximab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-05-03
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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

Primary outcomes:
measure: Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.
timeFrame: 28 days
measure: Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
timeFrame: 24 months
measure: Dose escalation: Frequency of dose interruptions and reductions, by treatment
timeFrame: 24 months
measure: Dose Escalation: Dose intensity by treatment
timeFrame: 24 months
measure: PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1
timeFrame: 24 months
Secondary outcomes:
measure: Dose escalation and Phase II: ORR by local review per RECIST 1.1
timeFrame: 24 months
measure: Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1
timeFrame: 24 months
measure: Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1
timeFrame: 24 months
measure: Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1
timeFrame: 24 months
measure: Phase II: DCR by BIRC per RECIST 1.1
timeFrame: 24 months
measure: Phase II: DoR by BIRC per RECIST 1.1
timeFrame: 24 months
measure: Phase II: PFS by BIRC per RECIST 1.1
timeFrame: 24 months
measure: Phase II: Overall survival (OS)
timeFrame: 24 months
measure: Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm
timeFrame: 5 months
measure: Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm
timeFrame: 5 months
measure: Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm
timeFrame: 5 months
measure: Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm
timeFrame: 5 months
measure: Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm
timeFrame: 5 months
measure: Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
timeFrame: 24 months
measure: Phase II: Frequency of dose interruptions and reductions, by treatment
timeFrame: 24 months
measure: Phase II: Dose intensity by treatment
timeFrame: 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
References: