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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07228247
- Acronym / sponsor ID
- 2025-251-GLOB1
- Conditions
- Solid Tumors, Adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 147 participants (estimated)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2025 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 14 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A(Phase I) | Experimental | Drug: HMPL-A251Dose Escalation |
| Part B(Phase IIa) | Experimental | Drug: HMPL-A251Dose Expansion/Dose Optimization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-A251Six 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. | Drug | Part A(Phase I) |
| HMPL-A251Participants 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. | Drug | Part B(Phase IIa) |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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.
10 secondary outcomes
Disease control rate (DCR)
Time frame: Approximately 2 years
Duration of response (DoR)
Time frame: Approximately 2 years
Time to response (TTR)
Time frame: Approximately 2 years
Progression-free survival (PFS)
Time frame: Approximately 2 years
Overall survival (OS)
Time frame: Approximately 2 years
Maximum plasma/serum concentration (Cmax)
Time frame: Cycle 1 and Cycle 3 (21-day cycle)
Time to maximum plasma/serum concentration (Tmax)
Time frame: Cycle 1 and Cycle 3 (21-day cycle)
Area under the plasma/serum concentration-time curve (AUC)
Time frame: Cycle 1 and Cycle 3 (21-day cycle)
Pre-dose plasma/serum concentration (Cmin)
Time frame: Each cycle (21-day cycle); from C9, every 4 cycles, through approximately 12 months
Immunogenicity of HMPL-A251
Time frame: Each cycle (21-day cycle), From C9, every 4 cycles, Approximately 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Florida Clinical Trials Group LLC (Plantation)
Plantation, United States
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HMPL-A251 in people with Solid Tumors, Adult, run by Hutchmed at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Approximately 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.