A Phase Ib/II ,Single Arm, Multi-Center, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of JAB-21822 in Advanced or Metastatic Non-small Cell Lung Cancer With a KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Allist Pharmaceuticals, Inc.
- Enrollment
- 104
- Locations
- 21
- Primary Endpoint
- Dose Escalation phase Number of participants with dose limiting toxicities (DLTs)
Overview
Brief Summary
Evaluate the safety and tolerability, drug levels, and clinical activity of JAB-21822 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors with KRAS p.G12C mutation and a serine/threonine kinase 11 (STK11) co-mutation.
Detailed Description
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 during Dose Escalation phase and preliminary antitumor activity in patients with NSCLC with concurrent KRAS G12C mutant and STK11 mutant and KEAP wild type either treatment naïve or at least one line prior therapy for advance disease during the expansion phase..
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Pathologically documented, locally-advanced or metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing.
- •STK11 co-mutation and KEAP1 Wild-Type (local confirmation)
- •Treatment naïve or have received at least 1 prior standard therapy for advanced NSCLC
Exclusion Criteria
- •Has CNS metastases or carcinomatous meningitis, except treated CNS metastases with no evidence of radiographic progression or hemorrhage for at least 28 days
- •Any severe and/or uncontrolled medical conditions
- •Active infection requiring systemic treatment within 7 days
- •Therapeutic radiation therapy within 3 weeks of study day 1
Arms & Interventions
Phase 1 ,Dose Exploration ,monotherapy
Dose escalation of JAB21822 will be administered as monotherapy to determine the MTD and RP2D
Intervention: JAB 21822 (Drug)
Phase 2, Dose Expansion, Part1 monotherapy
Part 1 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects with previously untreated advanced non-small cell lung cancer (NSCLC)
Intervention: JAB 21822 (Drug)
Phase 2 Dose Expansion, Part 2 monotherapy
Part 2 dose expansion is to evaluate the safety and clinical activity of JAB-21822 at RP2D in subjects who had received at least one previous line of systemic therapy for NSCLC
Intervention: JAB 21822 (Drug)
Outcomes
Primary Outcomes
Dose Escalation phase Number of participants with dose limiting toxicities (DLTs)
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
A DLT is defined as the clinically significant treatment-related adverse event or abnormal laboratory values assessment during the first 21 days of Cycle 1. It excludes adverse events (AEs) that are deemed clearly related to underlying disease, progression, or intercurrent illness.
Dose Escalation phase: Number of participants with adverse events
Time Frame: Up to 3 years
Patients will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria
Dose Expansion phase: Objective response rate (ORR)
Time Frame: Up to 3 years - from baseline to confirmed Progressive Disease per RECIST.
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1
Secondary Outcomes
- Dose Escalation and Dose Expansion phase: Duration of response (DOR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Overall Survival (OS)(Up to 3 years)
- Escalation and Dose Expansion phase：Area under the plasma concentration-time curve (AUC)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Progression-free survival (PFS)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Time to response (TTR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Plasma concentration (Cmax)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Time to achieve Cmax (Tmax)(Up to 3 Years)
- Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR)(Up to 3 years)
- Dose Escalation phase: Objective response rate (ORR)(Up to 3 years - from baseline to RECIST confirmed Progressive Disease)
- Dose Expansion phase: Number of participants with adverse events(Up to 3 years)