HMPL-306 for Isocitrate Dehydrogenase Deficiency

Recruiting at 10 trial locations

Overseen By Warren Moore, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hutchison Medipharma Limited

Must not be taking: QT-prolonging drugs

Disqualifiers: Pregnancy, Severe infection, Heart conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking medications that prolong the QT interval (a heart rhythm measure), you may not be eligible to participate.

What data supports the effectiveness of the drug HMPL-306 for treating isocitrate dehydrogenase deficiency?

While there is no direct data on HMPL-306, similar drugs targeting mutant isocitrate dehydrogenase (IDH) have shown promise in treating conditions like acute myeloid leukemia by inhibiting the abnormal enzyme activity caused by IDH mutations, which can lead to cancer cell growth. ^{1 2 3 4 5}

What makes the drug HMPL-306 unique for treating isocitrate dehydrogenase deficiency?

HMPL-306 is unique because it specifically targets mutant forms of the isocitrate dehydrogenase (IDH) enzymes, which are involved in the abnormal production of an oncometabolite (a harmful metabolic byproduct) called 2-hydroxyglutarate. This targeted approach is different from other treatments that may not specifically address the mutant enzymes responsible for the condition. ^{2 4 5 6 7}

Research Team

Bo Zhang

Principal Investigator

Hutchison Medipharma Limited

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors that have an IDH mutation and have worsened despite standard treatments. Participants must be in fairly good physical condition (ECOG status 0 or 1) and cannot be pregnant, breastfeeding, or have severe infections, certain heart conditions, life-threatening complications of leukemia, specific gastrointestinal or liver diseases, or inadequate organ function.

Inclusion Criteria

My cancer has returned or worsened after standard treatment and cannot be cured.

I am fully active or can carry out light work.

My cancer has an IDH mutation confirmed by a lab test.

Exclusion Criteria

I do not have a severe infection or unexplained fever over 38.3°C.

I have or had liver or gastrointestinal diseases.

Subjects who received an investigational agent <14 days prior to their first day of study drug administration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive HMPL-306 orally to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

4 weeks

Weekly visits for dose escalation monitoring

Dose Expansion

Participants receive HMPL-306 at the determined MTD/RP2D to evaluate safety and efficacy

Up to 36 months

Monthly visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• HMPL-306

Trial Overview The study is testing HMPL-306's safety and effectiveness on patients with IDH-mutated advanced solid tumors. It's an open-label trial meaning everyone knows what treatment they're getting. Researchers will look at how the body processes the drug (pharmacokinetics), its effects on the body (pharmacodynamics), and any signs of tumor shrinkage.

Participant Groups

Group I: Part 2 Dose Expansion Cohorts Experimental Treatment 1 Intervention

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

Group II: Part 1 Dose Escalation Cohorts Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Hutchison Medipharma Limited

Lead Sponsor

Trials

104

Recruited

14,000+

Dr. Weiguo Su

Hutchison Medipharma Limited

Chief Executive Officer since 2022

PhD in Chemistry from Harvard University, BSc in Chemistry from Fudan University

Dr. Karen Atkin

Hutchison Medipharma Limited

Chief Medical Officer since 2023

MD from Harvard Medical School

Hutchmed

Lead Sponsor

Trials

38

Recruited

6,700+

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Identification and Characterization of Small-Molecule Inhibitors of the R132H/R132H Mutant Isocitrate Dehydrogenase 1 Homodimer and R132H/Wild-Type Heterodimer. [2018]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Isocitrate dehydrogenase mutations in myeloid malignancies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Mutations in the isocitrate dehydrogenase 2 gene and IDH1 SNP 105C > T have a prognostic value in acute myeloid leukemia. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Isocitrate dehydrogenase 1 mutations in melanoma frequently co-occur with NRAS mutations. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Differentiating Inhibition Selectivity and Binding Affinity of Isocitrate Dehydrogenase 1 Variant Inhibitors. [2023]