Clinical trial NCT04762602: A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Isocitrate Dehydrogenase Gene Mutation
Keywords: Cholangiocarcinoma
Skeletal chondrosarcoma
Glioma
IDH Mutation
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Eligibility criteria: Key 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.

Key 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

Primary outcomes:
measure: Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days after first dose of study drug
measure: Part 1 and Part 2: Frequency and severity of AEs
timeFrame: From the first dose of the study drug to 37 days after the last dose of study drug
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Duration of response (DoR)
timeFrame: From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months
measure: Progression-free Survival (PFS)
timeFrame: 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
measure: Maximum serum drug concentration
timeFrame: PK weeks at screening through safety follow-up, assessed up to 36 months
measure: Time to maximum concentration
timeFrame: PK weeks at screening through safety follow-up, assessed up to 36 months
measure: Area under the concentration-time curve (AUC)
timeFrame: PK weeks at screening through safety follow-up, assessed up to 36 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital de la Santa creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Hutchison Medipharma Limited
name: Bo Zhang
role: STUDY_DIRECTOR
References: