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

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

Overview

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

Interventions

• 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.
• 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.

Primary outcome measures

• Maximum Tolerated Dose (MTD) [Time frame: Approximately 12 months]
• Recommended doses for expansion (RDE) [Time frame: Approximately 12 months]
• Overview of Treatment-emergent Adverse Events (TEAEs) [Time frame: Approximately 24 months]
• Objective Response Rate (ORR) [Time frame: 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 [Time frame: Approximately 12 months]

Secondary outcome measures (9)

• 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]
• Pharmacokinetic Analysis(Cmax) [Time frame: Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months]
• Pharmacokinetic Analysis(Tmax) [Time frame: Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months]
• Pharmacokinetic Analysis((AUC) [Time frame: Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months]
• To evaluate the immunogenicity of HMPL-A251 [Time frame: Each cycle(21-day cycle), From C9, every 4 cycles, Approximately 12 months]

Eligibility criteria

Inclusion criteria

• 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;

Exclusion criteria

• 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);

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• SCRI HealthONE — Denver
• BRCR Global — Plantation
• Florida Clinical Trials Group LLC (Plantation) — Plantation
• Florida Clinical Trials Group LLC (Tamarac) — Tamarac
• START New Jersey — East Brunswick
• Memorial Sloan Kettering Cancer Center — New York
• Cleveland Clinic Taussig Cancer Center — Cleveland
• Northwest Medical Specialties, PLLC — Tacoma

China · 7 centers

• Peking University First Hospital — Beijing
• Hunan Cancer Hospital — Changsha
• Sun Yat-sen University Cancer Center — Guangzhou
• The First Affiliated Hospital of Anhui Medical University — Hefei
• Fudan University Shanghai Cancer Center — Shanghai
• The First Hospital of China Medical University — Shenyang
• Henan Cancer Hospital — Zhengzhou

Identifiers

NCT: NCT07228247 · 2025-251-GLOB1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗