Clinical trial NCT06959615: A Phase I/IIa Study of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration
Official title: A Multicenter, Open Phase I/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Jacobio Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-06
Enrollment: 334
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, phase I/IIa to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of JAB-23E73 in patients with advanced solid tumors harboring KRAS mutations or amplification. The study consists of 2 phases: Phase 1 Dose Escalation and Phase IIa Dose Expansion.


Eligibility criteria: Inclusion Criteria:

1. Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer with evidence of KRAS gene alteration (including gene mutation and wild type amplification).
2. Able to provide an archived tumor tissue sample or fresh biopsy sample.
3. Life expectancy ≥3 months at the start of treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. ≥1 measurable lesion per RECIST v1.1.
6. Adequate organ function.

Exclusion Criteria:

1. Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
2. Previous treatment with rat sarcoma (RAS) targeting agents.
3. Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
4. Impaired cardiovascular function or clinically significant cardiac disease.
5. Mean QT interval corrected using Fridericia's formula (QTcF) \>470 msec.
6. Females who are pregnant or breastfeeding.

Primary outcomes:
measure: Phase 1: Number of participants with dose limiting toxicities (DLT)
timeFrame: Up to 21 days
measure: Phase 2a: Objective response rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase 1/2a: Safety and Tolerability
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73
timeFrame: Up to approximately 2 years
measure: Phase 1: ORR
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Phase 1/2a: Duration of Response (DoR)
timeFrame: Up to approximately 2 years
measure: Phase 2a: Overall Survival (OS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Taiyuan
country: China
facility: ShanXi Cancer Hospital
state: Shanxi
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: