A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations

Isocitrate Dehydrogenase Gene Mutation Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04762602
• Other study ID #: 2020-306-GLOB2
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 28, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: March 2024
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: September 30, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Isocitrate Dehydrogenase Gene Mutation

Intervention

Drug:
• HMPL-306
Administered orally QD in a 28-day continuous dosing treatment cycle

Locations

Country	Name	City	State
Spain	Hospital de la Santa creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Emory University	Atlanta	Georgia
United States	Houston Methodist	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer	Pittsburgh	Pennsylvania
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Hutchmed

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 28 days after first dose of study drug
Primary	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	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).	From first dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	Clinical Benefit Rate (CBR)	CBR is the proportion of subjects with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).	From first dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	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.	From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months
Secondary	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.	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
Secondary	Maximum serum drug concentration	Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306	PK weeks at screening through safety follow-up, assessed up to 36 months
Secondary	Time to maximum concentration	Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306	PK weeks at screening through safety follow-up, assessed up to 36 months
Secondary	Area under the concentration-time curve (AUC)	Blood samples will be obtained from all patients for determination of the AUC of HMPL-306	PK weeks at screening through safety follow-up, assessed up to 36 months