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

NCT04762602 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2020-306-GLOB2
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 11

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.

Conditions

Isocitrate Dehydrogenase Gene Mutation

Keywords

Cholangiocarcinoma; Skeletal chondrosarcoma; Glioma; IDH Mutation

Outcome Measures

Primary Outcomes (3)

• Part 1: Recommended Phase 2 Dose (RP2D) of HMPL-306

  RP2D determination took the following criteria under consideration: determination of maximum tolerated dose (MTD) achieved during the dose escalation part and assessment of safety, pharmacokinetics (PK) and pharmacodynamics (PD). The modified toxicity probability interval-2 design was used to perform dose escalation and planned to determine MTD/RP2D.

  From the first dose of study drug (Day 1) up to Day 28 of Cycle 1

• Part 1: Number of Patients With Dose-limiting Toxicities (DLTs)

  DLT:occurrence of any of following treatment-emergent adverse events (TEAEs) during DLT assessment window unless clearly unrelated to study drug/judged by investigator as not clinically significant: 1. Non-hematologic:TEAEs Grade \>=4, Grade 3 except those which recovered to Grade \<=1 within 3 days after supportive therapy administered for nausea,vomiting,diarrhea,constipation,fatigue,electrolyte imbalance;Grade 3 hypothyroidism, adrenal gland or pituitary insufficiency, and inflammatory reactions at tumor site \& Grade 3 hypertension downgraded to Grade \<=1 within 1 week with appropriate supportive therapy. 2. Hematologic:Grade \>=3 febrile neutropenia;Grade 4 neutropenia or thrombocytopenia;Grade 3 thrombocytopenia with clinically significant bleeding in addition to that requiring transfusion;Grade 4 anemia requiring a dose delay of \>=14 days. 3. Any life-threatening complication/abnormality not covered in National Cancer Institute Common Terminology Criteria for AEs version(v) 5.0.

  From the first dose of study drug (Day 1) up to Day 28 of Cycle 1

• Parts 1 and 2: Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)

  AE:unfavorable,unintended sign,symptom or disease temporally associated with use of study drug or other protocol-imposed drug, whether or not considered drug related. SAE:AE that resulted in death, was life threatening, inpatient hospitalization/prolongation of existing hospitalization, persistent/significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, important medical event that jeopardized patient and required medical/surgical intervention to prevent above outcome or signs, symptoms or clinical sequelae of suspected overdose of either study drug or a concomitant medication. TEAE:AE with onset on/after start of study drug until 30 days after last dose or prior to start of subsequent anti-tumor therapy, or AE with onset before start of study drug but worsened in severity after study drug administration or beyond 30 days after last dose or after start of subsequent anti-tumor therapy and treatment-related SAEs.

  From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 43 months for Part 1

Secondary Outcomes (9)

• Parts 1 and 2: Objective Response Rate (ORR)

  Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

• Parts 1 and 2: Disease Control Rate (DCR)

  Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

• Parts 1 and 2: Duration of Response (DoR)

  Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

• Parts 1 and 2: Time to Response (TTR)

  Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

• Parts 1 and 2: Progression-free Survival (PFS)

  Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

Study Arms (2)

Part 1 Dose Escalation Cohorts

EXPERIMENTAL

Patients from each cohort will be administered HMPL-306 orally QD

Drug: HMPL-306

Part 2 Dose Expansion Cohorts

EXPERIMENTAL

Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose

Drug: HMPL-306

Interventions

HMPL-306 DRUG

Administered orally QD in a 28-day continuous dosing treatment cycle

Part 1 Dose Escalation Cohorts; Part 2 Dose Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (11)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Hillman Cancer

Pittsburgh, Pennsylvania, 15232, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hospital de la Santa creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Glioma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Limitations and Caveats

The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns.

Results Point of Contact

• Title: Wade Clutson
• Organization: HUTCHMED Limited

HMPL306@hutch-med.com

973-306-4490

Study Officials

• Bo Zhang

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2021
• First Posted: February 21, 2021
• Study Start: February 28, 2021
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Locations

US (8); ES (3)