Clinical Trials /

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

NCT04699188

Description:

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 spartalizumab) 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
  • Official Title: A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Clinical Trial IDs

  • ORG STUDY ID: CJDQ443A12101
  • NCT ID: NCT04699188

Conditions

  • 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

Interventions

DrugSynonymsArms
JDQ443Arm A
TNO155Arm B
spartalizumabArm C

Purpose

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 spartalizumab) 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.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalJDQ443
  • JDQ443
Arm BExperimentalJDQ443 in combination with TNO155
  • JDQ443
  • TNO155
Arm CExperimentalJDQ443 in combination with spartalizumab
  • JDQ443
  • spartalizumab
Arm DExperimentalJDQ443 in combination with TNO155 and spartalizumab
  • JDQ443
  • TNO155
  • spartalizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid
             tumors

          -  Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of
             combinations

        Exclusion Criteria:

          -  Tumors harboring driver mutations that have approved therapies or tumors with known
             activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations, with exception of KRAS
             G12C mutations

          -  Active brain metastases

          -  Clinically significant cardiac disease or risk factors at screening
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Dose Escalation and Expansion: ORR per RECIST v1.1
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment
Time Frame:18 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment
Time Frame:18 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment
Time Frame:18 months
Safety Issue:
Description:
Measure:Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Expansion: Frequency of dose interruptions and reductions, by treatment
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Expansion: Dose intensity by treatment
Time Frame:24 months
Safety Issue:
Description:
Measure:Dose Expansion: Incidence and severity of AEs and SAEs by treatment
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • KRAS
  • KRAS G12C
  • Metastatic cancer
  • Advanced cancer
  • Enzyme inhibitor
  • PD-1
  • SHP2
  • Targeted therapy
  • Non-small-cell lung cancer
  • colorectal cancer
  • Molecular mechanisms of pharmacological action

Last Updated

April 12, 2021