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Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (KontRASt-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04699188
Recruitment Status : Recruiting
First Posted : January 7, 2021
Last Update Posted : May 6, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 5, 2021
First Posted Date  ICMJE January 7, 2021
Last Update Posted Date May 6, 2022
Actual Study Start Date  ICMJE February 24, 2021
Estimated Primary Completion Date August 21, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2022)
  • Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment [ Time Frame: 21 days ]
    A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
  • Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ 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).
  • Dose Escalation: Frequency of dose interruptions and reductions, by treatment [ Time Frame: 24 months ]
    Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
  • Dose Escalation: Dose intensity by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment [ Time Frame: 24 months ]
    Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI).
Original Primary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment [ Time Frame: 18 months ]
  • Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
  • Dose Escalation: Frequency of dose interruptions and reductions, by treatment [ Time Frame: 24 months ]
  • Dose Escalation: Dose intensity by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment [ Time Frame: 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2022)
  • Dose Escalation and Expansion: ORR per RECIST v1.1 [ Time Frame: 24 months ]
    Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI)
  • Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1 [ Time Frame: 24 months ]
    BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.
  • Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS) [ Time Frame: 24 months ]
    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. If patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. PFS will be summarized using the Kaplan-Meier method, along with 95% CI
  • Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1 [ 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. Estimates will use Kaplan-Meier method, and median DOR and corresponding 95% CI will be presented.
  • Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1 [ Time Frame: 24 months ]
    The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. It will be summarized along with the corresponding 95% exact CI
  • Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment [ Time Frame: Up to 24 months ]
    AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab
  • Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment [ Time Frame: Up to 24 months ]
    Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.
  • Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment [ Time Frame: Up to 24 months ]
    Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.
  • Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment [ Time Frame: Up to 24 months ]
    To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D
  • Dose Expansion: Dose intensity by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Frequency of dose interruptions and reductions, by treatment [ Time Frame: 24 months ]
    Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
  • Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment [ Time Frame: 21 days ]
    A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
  • Dose Expansion: Incidence and severity of AEs and SAEs by treatment [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Dose Escalation and Expansion: ORR per RECIST v1.1 [ Time Frame: 24 months ]
  • Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1 [ Time Frame: 24 months ]
  • Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS) [ Time Frame: 24 months ]
  • Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1 [ Time Frame: 24 months ]
  • Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1 [ Time Frame: 24 months ]
  • Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment [ Time Frame: 18 months ]
  • Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment [ Time Frame: 18 months ]
  • Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment [ Time Frame: 18 months ]
  • Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Frequency of dose interruptions and reductions, by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Dose intensity by treatment [ Time Frame: 24 months ]
  • Dose Expansion: Incidence and severity of AEs and SAEs by treatment [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Official Title  ICMJE A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Brief Summary This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • KRAS G12C Mutant Solid Tumors
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Colorectal
  • Cancer of Lung
  • Cancer of the Lung
  • Lung Cancer
  • Neoplasms, Lung
  • Neoplasms, Pulmonary
  • Pulmonary Cancer
  • Pulmonary Neoplasms
Intervention  ICMJE
  • Drug: JDQ443
    KRAS G12C inhibitor
  • Drug: TNO155
    SHP2 inhibitor
  • Biological: tislelizumab
    Anti PD1 antibody
Study Arms  ICMJE
  • Experimental: Arm A
    JDQ443
    Intervention: Drug: JDQ443
  • Experimental: Arm B
    JDQ443 in combination with TNO155
    Interventions:
    • Drug: JDQ443
    • Drug: TNO155
  • Experimental: Arm C
    JDQ443 in combination with tislelizumab
    Interventions:
    • Drug: JDQ443
    • Biological: tislelizumab
  • Experimental: Arm D
    JDQ443 in combination with TNO155 and tislelizumab
    Interventions:
    • Drug: JDQ443
    • Drug: TNO155
    • Biological: tislelizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2022)
375
Original Estimated Enrollment  ICMJE
 (submitted: January 5, 2021)
345
Estimated Study Completion Date  ICMJE August 21, 2024
Estimated Primary Completion Date August 21, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies
  • ECOG Performance Status of 0 or 1
  • At least one measurable lesion as defined by RECIST 1.1
  • Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations

Exclusion Criteria:

  • Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
  • Active brain metastases
  • Clinically significant cardiac disease or risk factors at screening
  • A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   China,   Denmark,   France,   Germany,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04699188
Other Study ID Numbers  ICMJE CJDQ443A12101
2020-004129-22 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP