HMPL-306 for Isocitrate Dehydrogenase Deficiency

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HMPL-306 for individuals with advanced or metastatic solid tumors that have a specific genetic mutation known as IDH. The main goals are to assess the treatment's safety, tolerability, and potential effectiveness against cancer. The trial consists of two parts: one to determine the optimal dose and another to evaluate its efficacy at that dose. Individuals whose cancer has returned or worsened after other treatments and who have an IDH mutation might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that HMPL-306 is likely to be safe for humans?

Research has shown that HMPL-306 is generally safe. Earlier studies demonstrated that patients tolerated the treatment without serious side effects. Reports indicate that patients responded well, suggesting it could be a safe option for those with advanced or spreading solid tumors with an IDH mutation. Although the trial remains in its early stages, these findings are promising for participants' safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about HMPL-306 because it targets isocitrate dehydrogenase (IDH) deficiency with a unique mechanism of action. Unlike other treatments that might focus on downstream effects, HMPL-306 directly inhibits mutated IDH enzymes, potentially reducing the harmful byproducts that contribute to cancer growth. This direct targeting approach could offer a new way to manage conditions linked to IDH mutations, possibly leading to more effective and targeted cancer therapies. Additionally, HMPL-306 is administered orally, which can be more convenient and less invasive compared to some existing treatments.

What evidence suggests that HMPL-306 might be an effective treatment for IDH deficiency?

Research has shown that HMPL-306, a new treatment targeting specific genetic changes called IDH mutations, holds promise for patients with these mutations. In studies on advanced solid tumors, this treatment has been safe and has shown signs of effectiveness. For example, in one study on patients with certain brain tumors, all participants experienced disease stabilization, meaning their tumors stopped growing, which is a positive result. Additionally, the treatment was well-tolerated, with no severe side effects reported. While more research is needed, these findings suggest HMPL-306 could be a valuable treatment option for certain cancers with IDH mutations. Participants in this trial will receive HMPL-306 in either the dose escalation or dose expansion cohorts to further evaluate its safety and effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Bo Zhang

Principal Investigator

Hutchison Medipharma Limited

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40516517/

than just another IDH inhibitor: Insights from the HMPL-306 ... The study highlights its manageable safety profile and robust preliminary efficacy, suggesting that it may be a valuable AML therapy.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666634025000029

HMPL-306 in relapsed or refractory IDH1- and/or IDH2- ... Hu et al. report the results of a phase 1 study of the dual IDH1/2 inhibitor HMPL-306 in relapsed/refractory IDH-mutant AML. The study ...

3. withpower.com withpower.com/trial/phase-1-1-2021-8b75f

HMPL-306 for Isocitrate Dehydrogenase Deficiency 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04764474

NCT04764474 | A Study of HMPL-306 in Advanced ... This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 administered orally.

5. asco.org asco.org/abstracts-presentations/ABSTRACT489350

Phase 1 study of HMPL-306, an inhibitor of mutant IDH1/ ... Efficacy signals were observed especially in LGG pts, in the efficacy evaluated set (N=14), objective response rate (ORR) was 7.1%, disease control rate was 100 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04762602

NCT04762602 | A Study of HMPL-306 in Advanced Solid ... 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39892383/

and/or IDH2-mutated acute myeloid leukemia: A phase 1 ... Conclusions: HMPL-306 showed an acceptable safety profile and promising preliminary efficacy. A phase 3, randomized study of HMPL-306 in R/R ...