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

• ClinicalTrials.gov Identifier: NCT04762602
• Recruitment Status: Active, not recruiting
• First Posted: February 21, 2021
• Last Update Posted: March 27, 2024
• Sponsor: Hutchmed
• Information provided by (Responsible Party): Hutchmed

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Isocitrate Dehydrogenase Gene Mutation	Drug: HMPL-306	Phase 1

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 28, 2021
• Estimated Primary Completion Date: March 30, 2024
• Estimated Study Completion Date: September 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 Dose Escalation Cohorts; Patients from each cohort will be administered HMPL-306 orally QD	Drug: HMPL-306; Administered orally QD in a 28-day continuous dosing treatment cycle
Experimental: Part 2 Dose Expansion Cohorts; Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose	Drug: HMPL-306; Administered orally QD in a 28-day continuous dosing treatment cycle

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 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).
2. Clinical Benefit Rate (CBR) [ Time Frame: 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).
3. Duration of response (DoR) [ Time Frame: 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.
4. Progression-free Survival (PFS) [ 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 ]
   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.
5. Maximum serum drug concentration [ Time Frame: 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
6. Time to maximum concentration [ Time Frame: 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
7. Area under the concentration-time curve (AUC) [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Sarcoma Oncology Research Center

Santa Monica, California, United States, 90403

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

UPMC Hillman Cancer

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

Houston Methodist

Houston, Texas, United States, 77030

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Spain

Hospital de la Santa creu i Sant Pau

Barcelona, Spain, 08025

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Sponsors and Collaborators

Hutchmed

Investigators

• Study Director: Marjo Hahka-Kemppinen, MD; Hutchmed

More Information

• Responsible Party: Hutchmed
• ClinicalTrials.gov Identifier: NCT04762602
• Other Study ID Numbers: 2020-306-GLOB2
• First Posted: February 21, 2021
• Last Update Posted: March 27, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hutchmed:

Cholangiocarcinoma; Skeletal chondrosarcoma; Glioma; IDH Mutation