A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Drug: JAB 21822
- Registration Number
- NCT05276726
- Lead Sponsor
- Jacobio Pharmaceuticals Co., Ltd.
- 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..
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 104
- 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
- ECOG 0-1
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2, Dose Expansion, Part1 monotherapy JAB 21822 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) Phase 1 ,Dose Exploration ,monotherapy JAB 21822 Dose escalation of JAB21822 will be administered as monotherapy to determine the MTD and RP2D Phase 2 Dose Expansion, Part 2 monotherapy JAB 21822 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
- Primary Outcome Measures
Name Time Method Dose Escalation phase Number of participants with dose limiting toxicities (DLTs) 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 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) 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 Outcome Measures
Name Time Method Dose Escalation and Dose Expansion phase: Duration of response (DOR) Up to 3 years DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per RECIST v1.1 or death due to any cause, whichever occurs first.
Dose Escalation and Dose Expansion phase: Overall Survival (OS) Up to 3 years Defined as time from first treatment to death by any cause
Escalation and Dose Expansion phase：Area under the plasma concentration-time curve (AUC) Up to 3 Years AUC of JAB-21822 will be measured by using plasma PK samples
Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) Up to 3 years PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per RECIST1.1 or death whichever occurs first
Dose Escalation and Dose Expansion phase: Time to response (TTR) Up to 3 years Defined as time from first treatment to first evidence of PR or CR
Dose Escalation and Dose Expansion phase: Plasma concentration (Cmax) Up to 3 Years Cmax of JAB-21822 will be measured by using plasma PK samples
Dose Escalation and Dose Expansion phase: Time to achieve Cmax (Tmax) Up to 3 Years Tmax of JAB-21822 will be measured by using plasma PK samples
Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR) Up to 3 years DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1
Dose Escalation phase: Objective response rate (ORR) Up to 3 years - from baseline to RECIST confirmed Progressive Disease ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1
Dose Expansion phase: Number of participants with adverse events Up to 3 years Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria
Trial Locations
- Locations (21)
Research site05
🇨🇳Xiamen, Fujian, China
Research site08
🇨🇳Beijing, Beijing, China
Research site02
🇨🇳Beijing, Beijing, China
Research site012
🇨🇳Changsha, Hunan, China
Research site03
🇨🇳Hubei, Wuhan, China
Research site09
🇨🇳Beijing, Beijing, China
Research site021
🇨🇳Beijing, Beijing, China
Research site01
🇨🇳Beijing, Beijing, China
Research site013
🇨🇳Beijing, Beijing, China
Research site010
🇨🇳Chongqing, Chongqing, China
Research site011
🇨🇳Shenzhen, Guangdong, China
Research site016
🇨🇳Nanning, Guangxi, China
Research site017
🇨🇳Shijiazhuang, Hebei, China
Research site018
🇨🇳Ha'erbin, Heilongjiang, China
Research site04
🇨🇳Zhengzhou, Henan, China
Research site015
🇨🇳Changchun, Jilin, China
Research site06
🇨🇳Shenyang, Liaoning, China
Research site07
🇨🇳Shenyang, Liaoning, China
Research site014
🇨🇳Hohhot, Neimenggu, China
Research site020
🇨🇳Xi'an, Shanxi, China
Research site019
🇨🇳Hangzhou, Zhejiang, China