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

Phase 2RecruitingNCT07228247

Hutchmed147 enrolled

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.

* 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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

147

Conditions

Solid Tumors, Adult

Interventions

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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);

Locations (11)

SCRI HealthONE

Denver, Colorado, United States

NOT_YET_RECRUITING

BRCR Global

Plantation, Florida, United States

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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).

Time frame: 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.

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

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.

Time frame: Approximately 12 months

Secondary Outcomes

Data from ClinicalTrials.gov

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