Clinical trial NCT06973564: JAB-23E73 in Adult Participants With Advanced Solid Tumors With KRAS Alteration
Official title: A Phase 1/2a, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of JAB-23E73 in Adult Patients With Advanced Solid Tumors With KRAS Alteration
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Jacobio Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-15
Enrollment: 294
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 and tolerability of JAB-23E73 in adult participants with advanced solid tumors

Detailed description: Study JAB-23E73-1002 is a multicenter, open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anticancer activity of JAB-23E73 as a single agent in adult patients with advanced solid tumors with KRAS alteration. This study consists of a Phase 1a dose-escalation, followed by Phase 1b dose-expansion and Phase 2a indication expansion. After completing dose-escalation, the MTD or preliminary RP2D of JAB-23E73 will be determined. The RP2D will be determined according to the safety, efficacy and PK data from phase 1b. The indication expansion phase will further explore the efficacy and safety in advanced KRAS-alternated tumors which consist of 3 cohorts: Cohort C1, the CRC cohort; Cohort C2, the PDAC cohort; and Cohort C3, other solid tumor cohort.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Participant must be ≥18 years of age at the time of signing the Informed Consent Form (ICF).
* Histologically or cytologically confirmed locally advanced or metastatic solid tumors that are not suitable for curative interventions.
* Patients must have KRAS alterations.
* Participants are required to provide an archived tumor sample.
* Patients with a life expectancy ≥3 months.
* ECOG performance status score of 0 or 1.
* Patients must have at least one measurable lesion as defined by RECIST v1.1.

Exclusion Criteria:

* Inability to swallow oral medications, or presence of gastrointestinal dysfunction or gastrointestinal disorders that may significantly alter the absorption of the study drug.
* Patients who have previously been treated with KRAS G12C inhibitors, KRAS G12D inhibitors, or pan/multi-KRAS inhibitors.
* Known serious allergy to JAB-23E73 or excipient.
* Patients with primary central nervous system tumors.
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures or medical intervention.
* QT interval\>470 msec.
* LVEF ≤50% assessed by ECHO or MUGA.

Primary outcomes:
measure: Dose Escalation (Phase 1a): Determine the Maximum tolerated dose (MTD) of JAB-23E73 monotherapy.
timeFrame: Up to 1 year
measure: Dose Escalation (Phase 1a): Evaluate the overall safety and tolerability of JAB-23E73.
timeFrame: Up to 2 years
measure: Dose Expansion/Optimization (Phase 1b): Determine the Recommended Phase 2 Dose (RP2D) of JAB-23E73 in patients with KRAS- alternated NSCLC or other selected tumors.
timeFrame: Up to 2 years
measure: Indication Expansion (Phase 2a): Evaluate the preliminary antitumor activity of JAB-23E73 monotherapy at the RP2D in patients with advanced or metastatic CRC, PDAC, and other solid tumors.
timeFrame: Up to 3 years
measure: Dose Expansion/Optimization (Phase 1b): Determine the RP2D of JAB-23E73 in patients with KRAS- alternated NSCLC or other selected tumors.
timeFrame: Up to 2 years
measure: Indication Expansion (Phase 2a): Evaluate the preliminary antitumor activity of JAB-23E73 monotherapy at the RP2D in patients with advanced or metastatic CRC, PDAC, and other solid tumors.
timeFrame: Up to 3 years
Secondary outcomes:
measure: Dose Escalation (Phase 1a): Overall Response Rate (ORR)
timeFrame: Up to 2 years
measure: Dose Escalation (Phase 1a): Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
timeFrame: Up to 2 years
measure: Dose Expansion/Optimization (Phase 1b): Overall Response Rate (ORR)
timeFrame: Up to 2 years
measure: Dose Expansion/Optimization (Phase 1b): Evaluate the overall safety and tolerability of JAB-23E73.
timeFrame: Up to 2 years
measure: Dose Expansion/Optimization (Phase 1b): Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
References: