HMPL-A830 in Solid Tumors
ConditionSolid Tumor, Adult
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorHutchmed
About this trial
This is a first-in-human (FIH), multicenter, open-label, phase I/Ⅱa clinical study of HMPL-A830 in participants with histologically or cytologically confirmed, unresectable, advanced, or metastatic solid tumors\*, who are refractory or progressed on/after available standard treatment. The study will be conducted in 2 parts:
Dose Escalation (Part A, Phase I), approximately 57 participants will be enrolled.
Dose Optimization (Part B, Phase IIa), approximately 90 participants will be enrolled.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Understood this study and are able to voluntarily sign the informed consent form (ICF);
Male or Female, Age ≥ 18 years;
Histological confirmed, unresectable, advanced or metastatic solid tumor
Participants must have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
Disqualifiers
Use 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
Major surgery within 28 days prior to the first dose of study drug
Active infection requiring systemic treatment
History of inflammatory gastrointestinal diseases
Trial design
Design model
Sequential
Treatments tested in this trial
HMPL-A830
DrugEnrolled participants with solid tumors will receive HMPL-A830 treatment in a dose escalation setting at 6 predefined dose levels
HMPL-A830
DrugParticipants will be randomized in a 1:1 ratio to receive treatment in two RDO levels. Randomization will be stratified by tumor types.
Treatment groups
147 Participants
are divided into 2 treatment groupsGroup A: Part A (Dose Escalation)Experimental treatment 1 intervention
Group B: Part B (Dose Optimization)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
DLTs
Number of Participants With of DLTs
Time frame
Approximately 12 months2
Overview of Treatment-emergent Adverse Events (TEAEs)
The number of participants with Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v6.0
Time frame
Approximately 12 months3
Objective Response Rate (ORR)
Assessed by investigators according to RECIST 1.1
Time frame
Approximately 24 months4
Recommended doses for phase II or III studies (RP2D or RP3D)
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 monthsSecondary outcomes
1
Disease control rate (DCR)
The DCR by RECIST 1.1
Time frame
Approximately 2 years2
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.
Time frame
Approximately 2 years3
Pharmacokinetic Analysis(Cmax)
Maximum plasma concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload)
Time frame
Approximately 2 years4
Pharmacokinetic Analysis (Cmin)
Trough concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload)
Time frame
Approximately 2 years Source ClinicalTrials.gov