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
Hutchmed
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.
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
Eligibility
- Age range
- 18+ years
- Sex
- All
- 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 (whiche…
Interventions
- DrugHMPL-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.
- DrugHMPL-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.
Locations (11)
- SCRI HealthONEDenver, Colorado
- BRCR GlobalPlantation, Florida
- Memorial Sloan Kettering Cancer CenterNew York, New York
- Cleveland Clinic Taussig Cancer CenterCleveland, Ohio
- Vanderbilt University Medical CenterNashville, Tennessee
- Peking University First HospitalBeijing