JAB-23E73 in Adult Participants With Advanced Solid Tumors With KRAS Alteration

Jacobio Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: JAB-23E73

Study type: Interventional

Funder types: Industry

Identifiers

NCT06973564

JAB-23E73-1002

Details and patient eligibility

About

This study is to evaluate the safety and tolerability of pan-KRAS inhibitor JAB-23E73 in adult participants with advanced solid tumors

Full 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.

Enrollment: 294 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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294 participants in 3 patient groups

Dose Escalation (Phase 1a)

Experimental group

Description:

Evaluate overall Safety, tolerability, and determine MTD of JAB-23E73 monotherapy.

Treatment:

Drug: JAB-23E73

Drug: JAB-23E73

Drug: JAB-23E73

Dose Expansion / Optimization Phase (Phase 1b)

Experimental group

Description:

Determine RP2D of JAB-23E73 in patients with KRAS-alternated NSCLC or other selected tumors

Treatment:

Drug: JAB-23E73

Drug: JAB-23E73

Drug: JAB-23E73

Indication Expansion (Phase 2a)

Experimental group

Description:

Evaluate the preliminary antitumor activity of JAB-23E73 monotherapy at the RP2D in patients with advanced or metastatic CRC, PDAC, and other solid tumors.

Treatment:

Drug: JAB-23E73

Drug: JAB-23E73

Drug: JAB-23E73