Solid Tumors, AdultPhase 1/2NCT07228247
A Phase Ⅰ/Ⅱa Study of HMPL-A251 in Participants With Advanced or Metastatic HER2-expressing Solid Tumors
A Phase 1/2 study testing HMPL-A251 in people with Solid Tumors, Adult, run by Hutchmed at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Adult
- What is being tested?
- HMPL-A251
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 16 Dec 2025to 31 Dec 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- An established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus.
- 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;
- 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);
Trial locations and contacts
15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 2 countries
United States8 sites, 8 recruiting
- Recruiting
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
WenWee Ma, 216-559-9815, keaneyh@ccf.org
- Recruiting
SCRI HealthONE
Denver, Colorado, 80218
Gerald Falchook, 940-365-6217, bianca.reyes@scri.com
- Not yet recruiting
START New Jersey
East Brunswick, New Jersey, 08816
Bruno Fang
- Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Vicky Makker
- Recruiting
BRCR Global
Plantation, Florida, 33322
Harshad Amin, 561-447-0614, alejandrop@brcrglobal.com
- Recruiting
Florida Clinical Trials Group LLC (Plantation)
Plantation, Florida, 33322
Harshad Amin, 772-297-3057, clinops@floridactg.com
- Not yet recruiting
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Jorge Chaves
- Not yet recruiting
Florida Clinical Trials Group LLC (Tamarac)
Tamarac, Florida, 33321
Chintan Ghandi
China7 sites, 7 recruiting
- Recruiting
Peking University First Hospital
Beijing
Shikai Wu, +86 18910715326, skywu4329@sina.com
Yu Fan
- Recruiting
Hunan Cancer Hospital
Changsha
Quchang Oyang, 0731-89762161, Oyqc1969@126.com
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou
Shusen Wang, 020-87342693, Wangshus@susucc.org.cn
- Recruiting
The First Affiliated Hospital of Anhui Medical University
Hefei
Yingying Du, 0551-65908511, duyy1980@126.com
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai
Xiaohua Wu, 18121299168, wu.xh@fudan.edu.cn
Jian Zhang
- Recruiting
The First Hospital of China Medical University
Shenyang
Funan Liu, 13609877906, lfn_clinical@126.com
- Recruiting
Henan Cancer Hospital
Zhengzhou
Min Yan, +86 157 1385 7388, ym200678@163.com
About this study
Official title: 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 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.
Read the detailed description
- 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
- Solid Tumors, Adult
- Being tested
- HMPL-A251
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-A251Drug
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-A251Drug
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 group | Role | What they receive |
|---|---|---|
| Part A(Phase I) | Experimental | Dose Escalation Receives: Drug: HMPL-A251 |
| Part B(Phase IIa) | Experimental | Dose Expansion/Dose Optimization Receives: Drug: HMPL-A251 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Approximately 12 months
Secondary outcomes (10)
Disease control rate (DCR)
The proportion of participants with BOR of confirmed CR, confirmed PR, or stable disease (SD) lasting at least 5 weeks.
Measured: Approximately 2 years
Duration of response (DoR)
Only applies to participants whose BOR is confirmed CR or PR and is defined as the time from the first occurrence of objective tumor response (CR or PR) to the date of first radiographic PD or death due to any cause.
Measured: Approximately 2 years
Time to response (TTR)
Only applies to participants whose BOR is confirmed CR or PR and is defined as the time from the first dose of study dose to the first occurrence of objective tumor response (CR or PR)
Measured: Approximately 2 years
Progression-free survival (PFS)
The time from the first dose of study drug to the date of first radiographic PD per RECIST v1.1 or death due to any cause, whichever occurs first.
Measured: Approximately 2 years
Overall survival (OS)
Every 12 weeks (± 7 days) until death, withdrawal of consent for follow-up, lost to follow-up or end of study, whichever occurs first.
Measured: Approximately 2 years
Maximum plasma/serum concentration (Cmax)
Observed maximum plasma/serum concentration of HMPL-A251, total anti-HER2 antibody, and HM5041609; only applies to Cycles 1 and 3.
Measured: Cycle 1 and Cycle 3 (21-day cycle)
Time to maximum plasma/serum concentration (Tmax)
Time to observed Cmax for HMPL-A251, total anti-HER2 antibody, and HM5041609
Measured: Cycle 1 and Cycle 3 (21-day cycle)
Area under the plasma/serum concentration-time curve (AUC)
Derived from the observed plasma/serum concentration-time data for HMPL-A251, total anti-HER2 antibody, and HM5041609 using noncompartmental analysis
Measured: Cycle 1 and Cycle 3 (21-day cycle)
Pre-dose plasma/serum concentration (Cmin)
Observed pre-dose plasma/serum concentration of HMPL-A251, total anti-HER2 antibody, and HM5041609.
Measured: Each cycle (21-day cycle); from C9, every 4 cycles, through approximately 12 months
Immunogenicity of HMPL-A251
Incidence of anti-drug antibody and neutralizing antibody against HMPL-A251
Measured: Each cycle (21-day cycle), From C9, every 4 cycles, Approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2025
- Study start16 Dec 2025
- Primary completion30 Nov 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumors, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 147 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07228247
- Sponsor's protocol ID
- 2025-251-GLOB1
- Status last verified
- Sep 2026
- First submitted
- 11 Nov 2025
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No