JAB-21822 in Combination With Cetuximab in Patients With Advanced CRC and Other Solid Tumors With KRAS G12C Mutation
Study Details
Study Description
Brief Summary
This study is to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of JAB-21822 in combination with cetuximab in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 in combination with cetuximab to determine the MTD and RP2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 is administered in combination with cetuximab during Dose Expansion phase in patients with advanced colorectal cancer，advanced small intestine cancer and advanced appendiceal cancer with KRAS p.G12C mutation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1b Dose Escalation Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab. |
Drug: JAB-21822
JAB-21822 administered orally as a tablet.
Drug: Cetuximab
Cetuximab administered as an intravenous (IV) infusion.
|
| Experimental: Phase 2 Dose Expansion, Cohort 1 Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. |
Drug: JAB-21822
JAB-21822 administered orally as a tablet.
Drug: Cetuximab
Cetuximab administered as an intravenous (IV) infusion.
|
| Experimental: Phase 2 Dose Expansion, Cohort 2 Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer. |
Drug: JAB-21822
JAB-21822 administered orally as a tablet.
Drug: Cetuximab
Cetuximab administered as an intravenous (IV) infusion.
|
Outcome Measures
Primary Outcome Measures
- 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 (TRAE) or abnormal laboratory values assessment during the first 21 days of (Cycle 1) and excludes events that are deemed clearly related to underlying disease, progression, or intercurrent illness.
- Dose Expansion phase: Overall response rate (ORR) [Up to 4 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.
Secondary Outcome Measures
- Dose Escalation and Dose Expansion phase: Number of participants with adverse events [Up to 4 years]
Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria.
- Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax) [Up to 4 years]
Cmax of JAB-21822 will be measured by using plasma PK samples.
- Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC) [Up to 4 years]
AUC of JAB-21822 will be measured by using plasma PK samples.
- Dose Expansion phase: Duration of response ( DOR ) [Up to 4 years]
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.
- Dose Escalation phase: Overall response rate (ORR) [Up to 4 years]
The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1.
- Dose Expansion phase: Disease Control Rate ( DCR ) [Up to 4 years]
DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1.
- Dose Expansion phase: Progression-free survival (PFS) [Up to 4 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must be able to provide an archived tumor sample
-
Histologically or cytologically confirmed advanced colorectal cancer, advanced small intestinal cancer and advanced appendiceal cancer with KRAS p.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 metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days
-
Active infection requiring systemic treatment within 14 days
-
Active HIV, HBV or HCV
-
Any severe and/or uncontrolled medical conditions
-
LVEF<50% assessed by ECHO
-
QT interval >470 msec
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research site01 | Beijing | Beijing | China | 100101 |
| 2 | Research site02 | Beijing | Beijing | China | 100101 |
| 3 | Research site12 | Beijing | Beijing | China | 100101 |
| 4 | Research site03 | Guangzhou | Guangdong | China | 510000 |
| 5 | Research site06 | Harbin | Heilongjiang | China | 150000 |
| 6 | Research site05 | Zhengzhou | Henan | China | 450000 |
| 7 | Research site07 | Zhengzhou | Henan | China | 450000 |
| 8 | Research site11 | Changsha | Hunan | China | 410000 |
| 9 | Research site09 | Nanjing | Jiangsu | China | 210000 |
| 10 | Research site08 | Nanchang | Jiangxi | China | 330000 |
| 11 | Research site04 | Changchun | Jilin | China | 130000 |
| 12 | Research site10 | Shenyang | Liaoning | China | 110000 |
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.- JAB-21822-1007