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

• Sponsor: Jacobio Pharmaceuticals Co., Ltd. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05276726
• Collaborator: (none)
• Enrollment: 104
• Locations: 21
• Arms: 3
• Anticipated Duration (Months): 42.1
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: JAB 21822	Phase 1/Phase 2

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
• Anticipated Enrollment: 104 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Anticipated Study Start Date: Aug 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Feb 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

3. 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

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

2. 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

3. 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.

4. 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

5. Dose Escalation and Dose Expansion phase: Overall Survival (OS) [Up to 3 years]

   Defined as time from first treatment to death by any cause

6. 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

7. 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

8. 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

9. 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

10. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research site08	Beijing	Beijing	China	100010
2	Research site09	Beijing	Beijing	China	100010
3	Research site021	Beijing	Beijing	China	100032
4	Research site02	Beijing	Beijing	China	100089
5	Research site01	Beijing	Beijing	China	100101
6	Research site013	Beijing	Beijing	China	101100
7	Research site010	Chongqing	Chongqing	China	400000
8	Research site05	Xiamen	Fujian	China	361000
9	Research site011	Shenzhen	Guangdong	China	518000
10	Research site016	Nanning	Guangxi	China	530000
11	Research site017	Shijiazhuang	Hebei	China	050000
12	Research site018	Ha'erbin	Heilongjiang	China	150000
13	Research site04	Zhengzhou	Henan	China	450000
14	Research site012	Changsha	Hunan	China	410000
15	Research site015	Changchun	Jilin	China	130000
16	Research site06	Shenyang	Liaoning	China	110000
17	Research site07	Shenyang	Liaoning	China	110000
18	Research site014	Hohhot	Neimenggu	China	010000
19	Research site020	Xi'an	Shanxi	China	710000
20	Research site03	Hubei	Wuhan	China	430060
21	Research site019	Hangzhou	Zhejiang	China	310000

Sponsors and Collaborators

• Jacobio Pharmaceuticals Co., Ltd.

Investigators

• Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jacobio Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05276726
• Other Study ID Numbers: JAB-21822-1003
• First Posted: Mar 11, 2022
• Last Update Posted: Aug 2, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

No Results Posted as of Aug 2, 2022