Description:
This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and
combination therapy in adult participants with advanced solid tumors harboring KRAS G12C
mutation.
Title
- Brief Title: JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
- Official Title: A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
Clinical Trial IDs
- ORG STUDY ID:
JAB-21822-1001
- NCT ID:
NCT05002270
Conditions
- Advanced Solid Tumor
- NSCLC
- CRC
Interventions
| Drug | Synonyms | Arms |
|---|
| JAB-21822 (KRAS G12C inhibitor) | | Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation |
| JAB-21822 (KRAS G12C inhibitor) | | Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion |
| JAB-21822 (KRAS G12C inhibitor) | | Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion |
| Cetuximab (EGFR inhibitor) | | Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion |
Purpose
This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and
combination therapy in adult participants with advanced solid tumors harboring KRAS G12C
mutation.
Detailed Description
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822
monotherapy to determine the MTD and PR2D during Dose Escalation phase; then to evaluate
preliminary antitumor activity when JAB-21822 administered alone and combination with
cetuximab during Dose Expansion phase in adult participants with advanced solid tumors
harboring KRAS G12C mutation.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation | Experimental | Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D | - JAB-21822 (KRAS G12C inhibitor)
|
| Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion | Experimental | JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity. | - JAB-21822 (KRAS G12C inhibitor)
|
| Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion | Experimental | JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity. | - JAB-21822 (KRAS G12C inhibitor)
- Cetuximab (EGFR inhibitor)
|
Eligibility Criteria
Inclusion Criteria:
- Participants must be able to provide an archived tumor sample
- Histologically or cytologically confirmed solid tumors with KRAS G12C mutation
- Must have received at least 1 prior standard therapy
- Must have at least 1 measurable lesion per RECIST v1.1
- Must have adequate organ function
- Must be able to swallow and retain orally administered medication
Exclusion Criteria:
- Has brain or spinal metastases, except if treated and no evidence of radiographic
progression or hemorrhage for at least 28 days
- Active infection requiring systemic treatment within 7 days
- Active HBV or HCV
- Any severe and/or uncontrolled medical conditions
- LVEF ≤50% assessed by ECHO or QTcF
- QT interval >470 msec
- Experiencing unresolved CTCAE 5.0 Grade >1 toxicities
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs) |
| Time Frame: | At the end of Cycle 1 (each cycle is 21 days) |
| Safety Issue: | |
| Description: | Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria |
Secondary Outcome Measures
| Measure: | Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax) |
| Time Frame: | Up to 4 years |
| Safety Issue: | |
| Description: | Cmax of JAB-21822 alone or JAB-21822 plus cetuximabn will be measured by using plasma PK samples |
| Measure: | Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC) |
| Time Frame: | Up to 4 years |
| Safety Issue: | |
| Description: | AUC of JAB-21822 alone or JAB-21822 plus cetuximab will be measured by using plasma PK samples |
| Measure: | Dose Escalation phase: Overall response rate (ORR) |
| Time Frame: | Up to 4 years - from baseline to RECIST confirmed Progressive Disease |
| Safety Issue: | |
| Description: | The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1. |
| Measure: | Dose Escalation phase: Duration of response ( DOR ) |
| Time Frame: | Up to 4 years |
| Safety Issue: | |
| Description: | DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first. |
| Measure: | Dose Escalation and Dose Expansion phase: Disease Control Rate ( DCR ) |
| Time Frame: | Up to 4 years |
| Safety Issue: | |
| Description: | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1 |
| Measure: | Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) |
| Time Frame: | Up to 4 years |
| Safety Issue: | |
| Description: | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per CTCAE v1.1 or death which occurs first |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Jacobio Pharmaceuticals Co., Ltd. |
Trial Keywords
- KRAS G12C Mutant Advanced Solid Tumor; NSCLC; CRC
Last Updated
August 12, 2021
