A Phase I/IIa Study of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration
- Registration Number
- NCT06959615
- Lead Sponsor
- Jacobio Pharmaceuticals Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 334
- 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).
- Able to provide an archived tumor tissue sample or fresh biopsy sample.
- Life expectancy ≥3 months at the start of treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- ≥1 measurable lesion per RECIST v1.1.
- Adequate organ function.
- Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
- Previous treatment with rat sarcoma (RAS) targeting agents.
- Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
- Impaired cardiovascular function or clinically significant cardiac disease.
- Mean QT interval corrected using Fridericia's formula (QTcF) >470 msec.
- Females who are pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 Dose Exploration JAB-23E73 Monotherapy, dose escalation Phase 2a Dose Expansion JAB-23E73 Monotherapy, dose expansion
- Primary Outcome Measures
Name Time Method Phase 1: Number of participants with dose limiting toxicities (DLT) Up to 21 days Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. DLTs will be defined as the occurrence of any of the toxicities as described in the protocol.
Phase 2a: Objective response rate (ORR) Up to approximately 2 years ORR is defined as the proportion of patients with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1.
- Secondary Outcome Measures
Name Time Method Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73 Up to approximately 2 years PK: Tmax of JAB-23E73
Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73 Up to approximately 2 years PK: AUC of JAB-23E73
Phase 1: ORR Up to approximately 2 years ORR is defined as the proportion of patients with a BOR of confirmed CR or confirmed PR per RECIST v1.1.
Phase 1/2a: Safety and Tolerability Up to approximately 2 years Incidence and severity of treatment-emergent Adverse Events (TEAEs), treatment-related Adverse Events (TRAEs) and serious Adverse Events (SAEs), including incidence and severity of findings in laboratory values, ECG, ECOG and vital signs.
Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73 Up to approximately 2 years PK: Cmax of JAB-23E73
Phase 1/2a: Time to Response (TTR) Up to approximately 2 years TTR is defined as the time from the date of first dose of study drug to first documentation of response as assessed by the investigator per RECIST v1.1
Phase 1/2a: Progression Free Survival (PFS) Up to approximately 2 years PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first.
Phase 1/2a: Disease Control Rate (DCR) Up to approximately 2 years DCR is defined as the proportion of patients with CR, PR, or stable disease (SD) as assessed by the investigator per RECIST v1.1
Phase 1/2a: Duration of Response (DoR) Up to approximately 2 years DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.
Phase 2a: Overall Survival (OS) Up to approximately 2 years OS is defined as the time from the date of first dose of study drug until the date of death from any cause.
Trial Locations
- Locations (4)
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
ShanXi Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China