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.
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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Administered orally QD in a 28-day continuous dosing treatment cycle
Sarcoma Oncology Research Center
Santa Monica, California, United States
Emory University
Atlanta, Georgia, United States
University of Iowa
Iowa City, Iowa, United States
Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
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.
Time frame: Up to 28 days after first dose of 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
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).
Time frame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
Clinical Benefit Rate (CBR)
CBR is the proportion of subjects with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).
Time frame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
Duration of response (DoR)
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 frame: From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months
Progression-free Survival (PFS)
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.
Time frame: 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
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University of Kentucky
Lexington, Kentucky, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 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
Hospital de la Santa creu i Sant Pau
Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain
...and 1 more locations
Maximum serum drug concentration
Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306
Time frame: PK weeks at screening through safety follow-up, assessed up to 36 months
Time to maximum concentration
Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306
Time frame: PK weeks at screening through safety follow-up, assessed up to 36 months
Area under the concentration-time curve (AUC)
Blood samples will be obtained from all patients for determination of the AUC of HMPL-306
Time frame: PK weeks at screening through safety follow-up, assessed up to 36 months