JAB-21822 in Combination With Cetuximab in Patients With Advanced CRC and Other Solid Tumors With KRAS G12C Mutation
- Conditions
- Advanced Colorectal CancerAppendiceal CancerSmall Intestinal Cancer
- Interventions
- Registration Number
- NCT05194995
- Lead Sponsor
- Jacobio Pharmaceuticals Co., Ltd.
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 48
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 Dose Expansion, Cohort 1 JAB-21822 Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. Phase 1b Dose Escalation JAB-21822 Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab. Phase 1b Dose Escalation Cetuximab Dose escalation of JAB-21822 to determine maximum tolerated dose of JAB-21822 in combination with cetuximab. Phase 2 Dose Expansion, Cohort 2 JAB-21822 Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer. Phase 2 Dose Expansion, Cohort 1 Cetuximab Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. Phase 2 Dose Expansion, Cohort 2 Cetuximab Enrollment into the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced small intestinal cancer and advanced appendiceal cancer.
- 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 (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
Name Time Method 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: 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 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: 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.
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 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: 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.
Trial Locations
- Locations (17)
Research site31
🇨🇳Beijing, Beijing, China
Research site01
🇨🇳Beijing, Beijing, China
Research site02
🇨🇳Beijing, Beijing, China
Research site12
🇨🇳Beijing, Beijing, China
Research site13
🇨🇳Nanning, Guangxi, China
Research site06
🇨🇳Harbin, Heilongjiang, China
Research site05
🇨🇳Zhengzhou, Henan, China
Research site07
🇨🇳Zhengzhou, Henan, China
Research site11
🇨🇳Changsha, Hunan, China
Research site18
🇨🇳Wuhan, Hubei, China
Research site29
🇨🇳Changsha, Hunan, China
Research site19
🇨🇳Hangzhou, Zhejiang, China
Research site09
🇨🇳Nanjing, Jiangsu, China
Research site23
🇨🇳Xi'an, Shanxi, China
Research site28
🇨🇳Shanghai, Shanghai, China
Research site08
🇨🇳Nanchang, Jiangxi, China
Research site16
🇨🇳Linyi, Shandong, China
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