Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.
- Conditions
- Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation
- Interventions
- Registration Number
- NCT05445843
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression \< 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).
- Detailed Description
This is a non-randomized, open-label, single-arm, multicenter, phase II study evaluating the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic KRAS G12C-mutated NSCLC.
The study will have 2 non-comparative cohorts that will recruit participants in parallel according to the following characteristics:
* Cohort A: participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status (N=90).
* Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation (N=30).
The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. One treatment cycle consists of 21 (±3) days.
Study completion is defined as the earliest occurrence of one of the following:
* The last participant completes last study visit (and the assessments associated with this visit have been documented and followed-up appropriately by the Investigator), dies, withdraws consent, or is lost to follow-up, whichever comes first.\]
* In the event of an early study termination decision, the date of that decision.
* Another clinical study becomes available that can continue to provide JDQ443 to study participants and all participants with ongoing treatment are transferred to that clinical study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 96
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A- PD-L1<1% JDQ443 Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status. Cohort B- PD-L1≥ 1% and STK11 mutation JDQ443 Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) as determined by the Investigator in Cohort A Up to approximately 24 months Overall Response Rate (ORR) is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort A
- Secondary Outcome Measures
Name Time Method Key Secondary Outcome Measure: Overall Response Rate (ORR) as determined by the Investigator in Cohort B Up to approximately 24 months Overall Response Rate (ORR) is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the Investigator in Cohort B
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JDQ443 in plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Area Under the Curve From Time Zero to the last measurable concentration sampling time at steady-state (AUClastss) of JDQ443 in plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Observed concentration at the end of a dosing interval at steady-state (Cmin,ss) of JDQ443 in plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Total body clearance (CL/F) of JDQ443 from the plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Number of adverse events and serious adverse events as assessed by CTCAE criteria Up to approximately 60 months An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Treatment emergent Adverse Event (TEAEs) in this study were events that started after the first dose of study treatment and until 30 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.Maximum concentration (Cmax) of JDQ443 in plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Time to reach maximum concentration at steady-state (Tmax,ss) of JDQ443 in plasma Up to approximately 24 months Blood samples will be collected for pharmacokinetics characterization.
Trial Locations
- Locations (2)
The Brown University Oncology Group
🇺🇸Providence, Rhode Island, United States
Novartis Investigative Site
🇬🇧Torquay, United Kingdom