A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations
- Conditions
- Isocitrate Dehydrogenase Gene Mutation
- Interventions
- Registration Number
- NCT04762602
- Lead Sponsor
- Hutchmed
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 90
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.
Key
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation Cohorts HMPL-306 Patients from each cohort will be administered HMPL-306 orally QD Part 2 Dose Expansion Cohorts HMPL-306 Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
- Primary Outcome Measures
Name Time Method Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs) 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 From the first dose of the study drug to 37 days after the last dose of study drug
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR) From first dose of study drug to the time of progressive disease, assessed up to 36 months CBR is the proportion of subjects with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).
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 PFS is defined as time from first dose date of study drug to date of progression or date of death from any cause, whichever occurred first.
Objective Response Rate (ORR) From first dose of study drug to the time of progressive disease, assessed up to 36 months ORR is defined as the proportion of subjects with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).
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 DoR defined as the time from the date of the first CR or PR to the first date of progressive disease (PD) or death from any cause.
Time to maximum concentration PK weeks at screening through safety follow-up, assessed up to 36 months Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306
Area under the concentration-time curve (AUC) PK weeks at screening through safety follow-up, assessed up to 36 months Blood samples will be obtained from all patients for determination of the AUC of HMPL-306
Maximum serum drug concentration PK weeks at screening through safety follow-up, assessed up to 36 months Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306
Trial Locations
- Locations (11)
Hospital de la Santa creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
UPMC Hillman Cancer
🇺🇸Pittsburgh, Pennsylvania, United States
Houston Methodist
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States