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

NCT07228247 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2025-251-GLOB1
• Study Type: interventional
• Target: 147
• Locations: 2 countries
• Sites: 11

Brief 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.

Conditions

Solid Tumors, Adult

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD)

  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

  Approximately 12 months

• Recommended doses for expansion (RDE)

  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.

  Approximately 12 months

• Overview of Treatment-emergent Adverse Events (TEAEs)

  All TEAEs will be graded according to NCI CTCAE v6.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA).

  Approximately 24 months

• Objective Response Rate (ORR)

  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.

  At least 6 weeks post dose of first participant up to approximately 24 months

• Recommended doses for phase II or III studies (RP2D or RP3D) of HMPL-A251

  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.

  Approximately 12 months

Secondary Outcomes (9)

• Disease control rate (DCR)

  Approximately 2 years

• Duration of response (DoR)

  Approximately 2 years

• Time to response (TTR)

  Approximately 2 years

• Progression-free survival (PFS)

  Approximately 2 years

• Overall survival (OS)

  Approximately 2 years

Study Arms (2)

Part A(Phase I)

EXPERIMENTAL

Dose Escalation

Drug: HMPL-A251

Part B(Phase IIa)

EXPERIMENTAL

Dose Expansion/Dose Optimization

Drug: HMPL-A251

Interventions

HMPL-A251 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 A(Phase I)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• An established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus.
• 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;
• 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);
• Baseline blood amylase or lipase exceeds the normal range and are judged by the investigators to be clinically significant;
• 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;
• 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);

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (11)

SCRI HealthONE

Denver, Colorado, 80218, United States

NOT YET RECRUITING

BRCR Global

Plantation, Florida, 33322, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: November 14, 2025
• Study Start: December 16, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 29, 2025

Record last verified: 2025-12

Locations

US (5); CN (6)