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

NCT07228247 · tracked via the Priya Life Science China tracker

Sponsor

Hutchmed

Phase

Phase 1/2

Started

2025-12-16

Last updated

2026-09-22

Condition(s) studied

Solid Tumors, Adult

Investigational drug(s) / intervention(s)

HMPL-A251HMPL-A251

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.

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.

Study summary

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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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 or strong inducers 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);

Primary outcome measure(s)

Maximum Tolerated Dose (MTD) — Approximately 12 months
At least three participants will be enrolled in each dose cohort. Bayesian optimal interval design with backfill (BF-BOIN) will be used to guide dose escalation and to determine the MTD of HMPL-A251
Recommended doses for expansion (RDE) — Approximately 12 months
The RDE will be selected by evaluating all available data from the following criteria under consideration: Determination of MTD achieved during the dose escalation part; Safety data obtained across all different doses tested; Tolerability data, such as chronic toxicities, discontinuations, or withdrawals for toxicity that occur beyond the DLT period; PK data collected at the time of evaluation; Preliminary efficacy data.
Overview of Treatment-emergent Adverse Events (TEAEs) — Approximately 24 months
All TEAEs will be graded according to NCI CTCAE v6.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA).
Objective Response Rate (ORR) — At least 6 weeks post dose of first participant up to approximately 24 months
ORR is defined as the proportion of participants with Best objective response (BOR) of confirmed complete response (CR) or partial response (PR), as per investigator's assessment according to RECIST v1.1.
Recommended doses for phase II or III studies (RP2D or RP3D) of HMPL-A251 — Approximately 12 months
The RP2D or RP3D will be selected by evaluating all available data from the following criteria under consideration: Determination of MTD achieved during the dose escalation part; Safety data obtained across all different doses tested; Tolerability data; PK data; efficacy data.

Trial sites (15)

Facility	City	Region	Status
SCRI HealthONE	Denver	Colorado	Recruiting
BRCR Global	Plantation	Florida	Recruiting
Florida Clinical Trials Group LLC (Plantation)	Plantation	Florida	Recruiting
Florida Clinical Trials Group LLC (Tamarac)	Tamarac	Florida	Not Yet Recruiting
START New Jersey	East Brunswick	New Jersey	Not Yet Recruiting
Memorial Sloan Kettering Cancer Center	New York	New York	Not Yet Recruiting
Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	Recruiting
Northwest Medical Specialties, PLLC	Tacoma	Washington	Not Yet Recruiting
Peking University First Hospital	Beijing	China	Recruiting
Hunan Cancer Hospital	Changsha	China	Recruiting
Sun Yat-sen University Cancer Center	Guangzhou	China	Recruiting
The First Affiliated Hospital of Anhui Medical University	Hefei	China	Recruiting
Fudan University Shanghai Cancer Center	Shanghai	China	Recruiting
The First Hospital of China Medical University	Shenyang	China	Recruiting
Henan Cancer Hospital	Zhengzhou	China	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07228247 on ClinicalTrials.gov ↗ ← All trials in China