Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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);

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A(Phase I)
Dose Escalation
  • Drug: 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.
Experimental
Part B(Phase IIa)
Dose Expansion/Dose Optimization
  • 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.

Recruiting Locations

SCRI HealthONE
Denver, Colorado 80218
Contact:
Gerald Falchook
940-365-6217
bianca.reyes@scri.com

BRCR Global
Plantation, Florida 33322
Contact:
Harshad Amin
561-447-0614
alejandrop@brcrglobal.com

Florida Clinical Trials Group LLC (Plantation)
Plantation, Florida 33322
Contact:
Harshad Amin
772-297-3057
clinops@floridactg.com

Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio 44195
Contact:
WenWee Ma
216-559-9815
keaneyh@ccf.org

More Details

Status
Recruiting
Sponsor
Hutchmed

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.