HMPL-A251 for adults with advanced or metastatic HER2-expressing solid tumors

A Phase Ⅰ/Ⅱa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HMPL-A251 in Participants With Advanced or Metastatic HER2-Expressing Solid Tumors

This trial will test a new drug called HMPL-A251 to see if it is safe and helps adults with unresectable or metastatic HER2-expressing solid tumors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 147 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hutchmed (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 11 sites (Denver, Colorado and 10 other locations)
• Trial ID: NCT07228247 on ClinicalTrials.gov

What this trial studies

This first-in-human, open-label phase I/IIa study gives HMPL-A251 as monotherapy to adults with previously treated, unresectable or metastatic HER2-expressing solid tumors. The study begins with dose-escalation to determine the maximum tolerated dose and/or recommended dose(s) for expansion, then uses expansion cohorts to characterize safety and preliminary anti-tumor activity at those doses. Key outcome measures include safety and tolerability, dose-limiting toxicities, and objective tumor response by RECIST v1.1, with enrolled patients required to have measurable disease and an ECOG performance status of 0–1. The protocol also screens for drug interactions and unresolved toxicities from prior therapies before enrollment.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed unresectable advanced or metastatic HER2-expressing solid tumors who have measurable disease, ECOG 0–1, adequate life expectancy, and prior treatment as allowed by the protocol.

Not a fit: Patients with uncontrolled type I diabetes or uncontrolled type II diabetes, those taking strong CYP3A4/P-gp/BCRP inhibitors, or those with unresolved toxicities from prior therapy (and certain abnormal baseline labs) are ineligible and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, HMPL-A251 could offer a new targeted treatment option that controls tumor growth for some patients with HER2-expressing solid tumors.

How similar studies have performed: Other HER2-targeted therapies have shown benefit in various HER2-positive cancers, but HMPL-A251 is a first-in-human agent and its activity in this setting is not yet established.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed unresectable advanced or metastatic disease.
2. Have at least one measurable lesion per RECIST v1.1;
3. Life expectancy ≥ 12 weeks;
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1;
5. Weight ≥ 35 kg;

Exclusion Criteria:

1. An established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus.
2. Use of strong inhibitors of cytochrome P450 3A4 enzyme (CYP3A4), and inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) within 5 elimination half-lives or 2 weeks (whichever is longer) before the first dose of study drug;
3. Toxicity from prior anti-tumor therapy has not recovered to Grade 1 or baseline prior to the first dose of study drug (except alopecia). Participants with chronic Grade 2 toxicities may be eligible after discussion between the investigator and Sponsor Medical Monitor (e.g., Grade 2 chemotherapy-induced neuropathy);
4. Baseline blood amylase or lipase exceeds the normal range and are judged by the investigators to be clinically significant;
5. Spinal cord compression, leptomeningeal disease, or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;
6. Major surgery within 28 days prior to the first dose of study drug. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of study drug(s);

Where this trial is running

Denver, Colorado and 10 other locations

• SCRI HealthONE — Denver, Colorado, United States (Not_yet_recruiting)
• BRCR Global — Plantation, Florida, United States (Not_yet_recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Not_yet_recruiting)
• Cleveland Clinic Taussig Cancer Center — Cleveland, Ohio, United States (Not_yet_recruiting)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Not_yet_recruiting)
• Peking University First Hospital — Beijing, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, China (Not_yet_recruiting)
• Fujian Cancer Hospital — Fujian, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, China (Recruiting)
• The First Affiliated Hospital of Anhui Medical University — Hefei, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, China (Not_yet_recruiting)

Conditions Solid Tumors, Adult