A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: JAB 21822

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 Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd; Phone Number: 021-80423288; Email: zhenhua.gong@allist.com.cn
• Study Contact Backup: Name: Wang Jie Wang Jie M.D.; Phone Number: 010-87788029; Email: zlhuxi@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100101
      • Recruiting
      • Research site01
      • Contact: Wang Jie Wang Jie M.D., M.D.; Phone Number: 010-87788029; Email: zlhuxi@163.com
    • Beijing, Beijing, China, 100010
      • Not yet recruiting
      • Research site08
    • Beijing, Beijing, China, 100010
      • Not yet recruiting
      • Research site09
    • Beijing, Beijing, China, 100032
      • Not yet recruiting
      • Research site021
    • Beijing, Beijing, China, 100089
      • Not yet recruiting
      • Research site02
    • Beijing, Beijing, China, 101100
      • Not yet recruiting
      • Research site013
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Not yet recruiting
      • Research site010
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Not yet recruiting
      • Research site05
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Not yet recruiting
      • Research site011
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • Not yet recruiting
      • Research site016
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Not yet recruiting
      • Research site017
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China, 150000
      • Not yet recruiting
      • Research site018
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Not yet recruiting
      • Research site04
  • Hunan
    • Changsha, Hunan, China, 410000
      • Not yet recruiting
      • Research site012
  • Jilin
    • Changchun, Jilin, China, 130000
      • Not yet recruiting
      • Research site015
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Not yet recruiting
      • Research site06
    • Shenyang, Liaoning, China, 110000
      • Not yet recruiting
      • Research site07
  • Neimenggu
    • Hohhot, Neimenggu, China, 010000
      • Not yet recruiting
      • Research site014
  • Shanxi
    • Xi'an, Shanxi, China, 710000
      • Not yet recruiting
      • Research site020
  • Wuhan
    • Hubei, Wuhan, China, 430060
      • Not yet recruiting
      • Research site03
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Research site019

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically documented, locally-advanced or metastatic NSCLC with KRAS p.G12C mutation identified through molecular testing.
2. STK11 co-mutation and KEAP1 Wild-Type (local confirmation)
3. Treatment naïve or have received at least 1 prior standard therapy for advanced NSCLC
4. ECOG 0-1

Exclusion Criteria:

1. Has CNS metastases or carcinomatous meningitis, except treated CNS metastases with no evidence of radiographic progression or hemorrhage for at least 28 days
2. Any severe and/or uncontrolled medical conditions
3. Active infection requiring systemic treatment within 7 days
4. Therapeutic radiation therapy within 3 weeks of study day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 ,Dose Exploration ,monotherapy; Dose escalation of JAB21822 will be administered as monotherapy to determine the MTD and RP2D	Drug: JAB 21822; Administered orally
Experimental: 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)	Drug: JAB 21822; Administered orally
Experimental: 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	Drug: JAB 21822; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation phase Number of participants with dose limiting toxicities (DLTs)	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.	At the end of Cycle 1 (each cycle is 21 days)
Dose Escalation phase: Number of participants with adverse events	Patients will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria	Up to 3 years
Dose Expansion phase: Objective response rate (ORR)	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1	Up to 3 years - from baseline to confirmed Progressive Disease per RECIST.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation phase: Objective response rate (ORR)	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1	Up to 3 years - from baseline to RECIST confirmed Progressive Disease
Dose Escalation and Dose Expansion phase: Progression-free survival (PFS)	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	Up to 3 years
Dose Escalation and Dose Expansion phase: Duration of response (DOR)	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.	Up to 3 years
Dose Escalation and Dose Expansion phase: Disease Control Rate (DCR)	DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1	Up to 3 years
Dose Escalation and Dose Expansion phase: Overall Survival (OS)	Defined as time from first treatment to death by any cause	Up to 3 years
Dose Escalation and Dose Expansion phase: Time to response (TTR)	Defined as time from first treatment to first evidence of PR or CR	Up to 3 years
Dose Expansion phase: Number of participants with adverse events	Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria	Up to 3 years
Dose Escalation and Dose Expansion phase: Plasma concentration (Cmax)	Cmax of JAB-21822 will be measured by using plasma PK samples	Up to 3 Years
Dose Escalation and Dose Expansion phase: Time to achieve Cmax (Tmax)	Tmax of JAB-21822 will be measured by using plasma PK samples	Up to 3 Years
Escalation and Dose Expansion phase：Area under the plasma concentration-time curve (AUC)	AUC of JAB-21822 will be measured by using plasma PK samples	Up to 3 Years

Collaborators and Investigators

• Sponsor: Allist Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: JAB-21822-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No