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.
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
Drug | Synonyms | Arms |
---|
JDQ443 | | Arm A |
TNO155 | | Arm B |
spartalizumab | | Arm 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
Name | Type | Description | Interventions |
---|
Arm A | Experimental | JDQ443 | |
Arm B | Experimental | JDQ443 in combination with TNO155 | |
Arm C | Experimental | JDQ443 in combination with spartalizumab | |
Arm D | Experimental | JDQ443 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
June 23, 2021