A Multicenter, Open-Label, Phase I Study Evaluating the Safety and Tolerability of HMPL-306 in Subjects With Advanced or Metastatic Solid Tumors With IDH Mutations
Overview
- Phase
- Phase 1
- Intervention
- HMPL-306
- Conditions
- Isocitrate Dehydrogenase Gene Mutation
- Sponsor
- Hutchmed
- Enrollment
- 42
- Locations
- 11
- Primary Endpoint
- Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
- Status
- Terminated
- Last Updated
- 7 months ago
Overview
Brief Summary
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in advanced or metastatic solid tumors with IDH mutation.
Detailed Description
HMPL-306 is a dual IDH1/2 inhibitor This is a phase 1, open-label, multicenter study to evaluate the safety and tolerability of HMPL-306 administered orally in the treatment of subjects with advanced or metastatic solid tumors with IDH mutation. The study consists of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The dose escalation part will determine the MTD/RP2D. The dose expansion part will administer the MTD/RP2D to mIDH-positive solid tumor malignancies including, but not limited to, cholangiocarcinoma, skeletal chondrosarcoma, low-grade glioma, perioperative low-grade glioma
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
- •Subjects aged ≥18 years.
- •ECOG performance status 0 or 1
- •Subjects must have a documented IDH mutation per immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) testing of tumor tissue.
- •Subjects must have histologically or cytologically documented, advanced or metastatic solid malignancy of any type that has recurred or progressed on available standard treatment and for which no curative therapy exists.
Exclusion Criteria
- •Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
- •Subjects who received an investigational agent \<14 days prior to their first day of study drug administration
- •Subjects who are pregnant or breastfeeding
- •Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever \>38.3°C during screening visits or on their first day of study drug administration.
- •Subjects with some current or prior heart conditions
- •Subjects taking medications that are known to prolong the QT interval may not be eligible
- •Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
- •Some subjects with some current or prior gastrointestinal or liver diseases
- •Subjects with inadequate organ function as defined by the protocol
Arms & Interventions
Part 1 Dose Escalation Cohorts
Patients from each cohort will be administered HMPL-306 orally QD
Intervention: HMPL-306
Part 2 Dose Expansion Cohorts
Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
Intervention: HMPL-306
Outcomes
Primary Outcomes
Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days after first dose of study drug
DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
Part 1 and Part 2: Frequency and severity of AEs
Time Frame: From the first dose of the study drug to 37 days after the last dose of study drug
Secondary Outcomes
- Clinical Benefit Rate (CBR)(From first dose of study drug to the time of progressive disease, assessed up to 36 months)
- Progression-free Survival (PFS)(From first dose of study drug to the time of progressive disease or death due to any causes, whichever comes first, assessed up to 36 months)
- Objective Response Rate (ORR)(From first dose of study drug to the time of progressive disease, assessed up to 36 months)
- Duration of response (DoR)(From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months)
- Time to maximum concentration(PK weeks at screening through safety follow-up, assessed up to 36 months)
- Area under the concentration-time curve (AUC)(PK weeks at screening through safety follow-up, assessed up to 36 months)
- Maximum serum drug concentration(PK weeks at screening through safety follow-up, assessed up to 36 months)