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Trial record 1 of 1 for:    CJDQ443E12101
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Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (KontRASt-03)

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ClinicalTrials.gov Identifier: NCT05358249
Recruitment Status : Recruiting
First Posted : May 3, 2022
Last Update Posted : February 9, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
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 Drug: JDQ443 Drug: trametinib Drug: Ribociclib Biological: cetuximab Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 346 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 24, 2022
Estimated Primary Completion Date : May 5, 2027
Estimated Study Completion Date : June 16, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: JDQ443+trametinib
JDQ443 in combination with trametinib
 Drug: JDQ443
KRAS G12C inhibitor, oral

Drug: trametinib
MEK inhibitor, oral
Other Name: TMT212
Experimental: JDQ443+ribociclib
JDQ443 in combination with ribociclib
 Drug: JDQ443
KRAS G12C inhibitor, oral

Drug: Ribociclib
CDK4/6 inhibitor, oral
Other Name: LEE011
Experimental: JDQ443+cetuximab
JDQ443 in combination with cetuximab
 Drug: JDQ443
KRAS G12C inhibitor, oral

Biological: cetuximab
EGFR inhibitor, intravenous


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05358249


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Massachusetts
Massachusetts General Hospital . Recruiting
Boston, Massachusetts, United States, 02114
Contact: Aaron Paul Doss       APAULDOSS@mgh.harvard.edu   
Principal Investigator: Rebecca Heist         
Dana Farber Cancer Institute Dept.of DFCI Recruiting
Boston, Massachusetts, United States, 02215
Contact: Brian Schwalm       brian_schwalm@dfci.harvard.edu   
Principal Investigator: Jia Luo         
United States, New York
NYU School of Medicine Langone Health Recruiting
New York, New York, United States, 10015
Contact: Sasha Richardson    212-731-5662    sasha.richardson@nyulangone.org   
Principal Investigator: Janice Mehnert         
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
France
Novartis Investigative Site Recruiting
Bordeaux, France, 33076
Novartis Investigative Site Recruiting
Lyon, France, 69373
Germany
Novartis Investigative Site Recruiting
Freiburg, Germany, 79106
Novartis Investigative Site Recruiting
Ulm, Germany, 89081
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 168583
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05358249    
Other Study ID Numbers: CJDQ443E12101
2021-006196-42 ( EudraCT Number )
First Posted: May 3, 2022    Key Record Dates
Last Update Posted: February 9, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
KRAS G12C
targeted therapy
NSCLC
CRC
advanced solid tumors
 JDQ443
trametinib
ribociclib
cetuximab
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
 Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Trametinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action