A Phase Ⅰ/Ⅱa Study of HMPL-A251 in Participants With Advanced or Metastatic HER2-expressing Solid Tumors

NCT ID: NCT07228247

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-16

Study Completion Date

2028-12-31

Brief Summary

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This is a first-in-human (FIH), phase Ⅰ/Ⅱa, open-label, multicenter clinical study of HMPL-A251 monotherapy in adult participants with unresectable, advanced or metastatic HER2-expressing solid tumors.

Detailed Description

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* To evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of HMPL-A251 in participants with previously treated HER2+ solid tumors
* To characterize the safety and preliminary efficacy of HMPL-A251 at RDEs to determine recommended dose(s) for phase 2 (RP2D) or phase 3 (RP3D) in participants with selected HER2-expressing solid tumors

Conditions

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Solid Tumors, Adult

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A(Phase I)

Dose Escalation

Group Type EXPERIMENTAL

HMPL-A251

Intervention Type DRUG

Six dose cohorts are planned for the Dose Escalation phase; at least three participants with solid tumors will be enrolled in each dose cohort. Bayesian optimal interval design with backfill (BF-BOIN, Zhao, 2023) will be used to guide dose escalation and determine the MTD and/or RDE of HMPL-A251. All study participants will receive HMPL-A251 as IV infusion until PD, intolerable toxicity, or other protocol-specified criteria for ending study treatment, whichever occurs first.

Part B(Phase IIa)

Dose Expansion/Dose Optimization

Group Type EXPERIMENTAL

HMPL-A251

Intervention Type DRUG

Participants will be randomized in a 1:1 ratio to receive treatment in two RDEs levels (approximately 15 participants per dose level) for each cohort. All study participants will receive HMPL-A251 as IV infusion until PD, intolerable toxicity, or other protocol-specified criteria for ending study treatment, whichever occurs first.

Interventions

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HMPL-A251

Six dose cohorts are planned for the Dose Escalation phase; at least three participants with solid tumors will be enrolled in each dose cohort. Bayesian optimal interval design with backfill (BF-BOIN, Zhao, 2023) will be used to guide dose escalation and determine the MTD and/or RDE of HMPL-A251. All study participants will receive HMPL-A251 as IV infusion until PD, intolerable toxicity, or other protocol-specified criteria for ending study treatment, whichever occurs first.

Intervention Type DRUG

HMPL-A251

Participants will be randomized in a 1:1 ratio to receive treatment in two RDEs levels (approximately 15 participants per dose level) for each cohort. All study participants will receive HMPL-A251 as IV infusion until PD, intolerable toxicity, or other protocol-specified criteria for ending study treatment, whichever occurs first.

Intervention Type DRUG

Eligibility Criteria

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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);
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hutchmed

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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SCRI HealthONE

Denver, Colorado, United States

Site Status NOT_YET_RECRUITING

BRCR Global

Plantation, Florida, United States

Site Status NOT_YET_RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status NOT_YET_RECRUITING

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status NOT_YET_RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

Peking University First Hospital

Beijing, , China

Site Status NOT_YET_RECRUITING

Hunan Cancer Hospital

Changsha, , China

Site Status NOT_YET_RECRUITING

Fujian Cancer Hospital

Fujian, , China

Site Status NOT_YET_RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, , China

Site Status RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, , China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, , China

Site Status NOT_YET_RECRUITING

Countries

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United States China

Facility Contacts

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Gerald Falchook

Role: primary

Harshad Amin

Role: primary

Vicky Makker

Role: primary

WenWee Ma

Role: primary

Brent Rexer

Role: primary

Shikai Wu

Role: primary

Quchang Oyang

Role: primary

Fan Wu

Role: primary

Shusen Wang

Role: primary

Yingying Du

Role: primary

Min Yan

Role: primary

Other Identifiers

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2025-251-GLOB1

Identifier Type: -

Identifier Source: org_study_id