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NCT Number: NCT05358249

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

KRAS G12C Mutant Solid Tumors Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Non-small Cell Lung Colonic Diseases Colorectal Cancer Colorectal Carcinoma Colorectal Neoplasms Colorectal Tumors Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Neoplasms, Colorectal Non-small Cell Lung Cancer Non-small Cell Lung Carcinoma Nonsmall Cell Lung Cancer Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Leuven, Belgium

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

JDQ443

Drug

KRAS G12C inhibitor, oral

Trametinib

Drug

MEK inhibitor, oral

Other names: TMT212

Ribociclib

Drug

CDK4/6 inhibitor, oral

Other names: LEE011

Cetuximab

Biological

EGFR inhibitor, intravenous

Primary outcomes

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

    Time frame: 28 days

    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.

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

    Time frame: 24 months

    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).

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

    Time frame: 24 months

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

  4. Dose Escalation: Dose intensity by treatment

    Time frame: 24 months

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

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

    Time frame: 24 months

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

Secondary outcomes

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

    Time frame: 24 months

    ORR is the proportion of patients with a BOR of CR or PR.

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

    Time frame: 24 months

    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.

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

    Time frame: 24 months

    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.

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

    Time frame: 24 months

    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.

  5. Phase II: DCR by BIRC per RECIST 1.1

    Time frame: 24 months

    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.

  6. Phase II: DoR by BIRC per RECIST 1.1

    Time frame: 24 months

    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.

  7. Phase II: PFS by BIRC per RECIST 1.1

    Time frame: 24 months

    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.

  8. Phase II: Overall survival (OS)

    Time frame: 24 months

    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.

  9. Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm

    Time frame: 5 months

    The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)

  10. Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm

    Time frame: 5 months

    Observed concentration at the end of a dosing interval (taken directly before next administration)

  11. Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm

    Time frame: 5 months

    The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)

  12. Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm

    Time frame: 5 months

    The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

  13. Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm

    Time frame: 5 months

    The AUC from time zero to infinity (mass x time x volume-1)

  14. Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment

    Time frame: 24 months

    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).

  15. Phase II: Frequency of dose interruptions and reductions, by treatment

    Time frame: 24 months

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

  16. Phase II: Dose intensity by treatment

    Time frame: 24 months

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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: KontRASt-03

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
May 3, 2022
Registry last updated
Jun 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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