Clinical trial NCT05194995: JAB-21822 in Combination With Cetuximab in Patients With Advanced CRC and Other Solid Tumors With KRAS G12C Mutation
Official title: A Phase Ib/II Trial of JAB-21822 in Combination With Cetuximab in Patients With Advanced Colorectal Cancer, Small Intestine Cancer and Appendiceal Cancer With KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Colorectal Cancer
Small Intestinal Cancer
Appendiceal Cancer
Lead sponsor: Allist Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Dose Escalation phase: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Dose Expansion phase: Overall response rate (ORR)
timeFrame: Up to 4 years - from baseline to RECIST confirmed Progressive Disease
Secondary outcomes:
measure: Dose Escalation and Dose Expansion phase: Number of participants with adverse events
timeFrame: Up to 4 years
measure: Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax)
timeFrame: Up to 4 years
measure: Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to 4 years
measure: Dose Expansion phase: Duration of response ( DOR )
timeFrame: Up to 4 years
measure: Dose Escalation phase: Overall response rate (ORR)
timeFrame: Up to 4 years
measure: Dose Expansion phase: Disease Control Rate ( DCR )
timeFrame: Up to 4 years
measure: Dose Expansion phase: Progression-free survival (PFS)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research site31
state: Beijing
city: Beijing
country: China
facility: Research site01
state: Beijing
city: Beijing
country: China
facility: Research site02
state: Beijing
city: Beijing
country: China
facility: Research site12
state: Beijing
city: Nanning
country: China
facility: Research site13
state: Guangxi
city: Harbin
country: China
facility: Research site06
state: Heilongjiang
city: Zhengzhou
country: China
facility: Research site05
state: Henan
city: Zhengzhou
country: China
facility: Research site07
state: Henan
city: Wuhan
country: China
facility: Research site18
state: Hubei
city: Changsha
country: China
facility: Research site11
state: Hunan
city: Changsha
country: China
facility: Research site29
state: Hunan
city: Nanjing
country: China
facility: Research site09
state: Jiangsu
city: Nanchang
country: China
facility: Research site08
state: Jiangxi
city: Linyi
country: China
facility: Research site16
state: Shandong
city: Shanghai
country: China
facility: Research site28
state: Shanghai
city: Xi'an
country: China
facility: Research site23
state: Shanxi
city: Hangzhou
country: China
facility: Research site19
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Shen Lin Master of medicine
role: PRINCIPAL_INVESTIGATOR
References: