Solid Tumor, Adult
Conditions
Brief summary
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.
Detailed description
Part A: To evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for optimization (RDO) of HMPL-A830 in previously treated participants with solid tumors. Part B: To characterize the safety, tolerability, and preliminary efficacy of HMPL-A830 at RDO(s) to determine recommended dose(s) for phase 2 (RP2D) or phase 3 (RP3D) in participants with selected solid tumors
Interventions
DRUGHMPL-A830
Enrolled participants with solid tumors will receive HMPL-A830 treatment in a dose escalation setting at 6 predefined dose levels
Sponsors
Hutchmed
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Understood this study and are able to voluntarily sign the informed consent form (ICF); 2. Male or Female, Age ≥ 18 years; 3. Histological confirmed, unresectable, advanced or metastatic solid tumor 4. Participants must have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 5. Life expectancy ≥ 12 weeks 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
Exclusion criteria
1. 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 2. Major surgery within 28 days prior to the first dose of study drug 3. Active infection requiring systemic treatment 4. History of inflammatory gastrointestinal diseases 5. Known hypersensitivity to any component of HMPL-A830 6. Pregnant (positive pregnancy test) or lactating;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLTs | Approximately 12 months | Number of Participants With of DLTs |
| Overview of Treatment-emergent Adverse Events (TEAEs) | Approximately 12 months | The number of participants with Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v6.0 |
| Objective Response Rate (ORR) | Approximately 24 months | Assessed by investigators according to RECIST 1.1 |
| Recommended doses for phase II or III studies (RP2D or RP3D) | Approximately 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Approximately 2 years | The DCR by RECIST 1.1 |
| Progression-free survival (PFS) | Approximately 2 years | 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. |
| Pharmacokinetic Analysis(Cmax) | Approximately 2 years | Maximum plasma concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload) |
| Pharmacokinetic Analysis (Cmin) | Approximately 2 years | Trough concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload) |
| Pharmacokinetic Analysis(Tmax) | Approximately 2 years | Time to reach maximum concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload) |
| Pharmacokinetic Analysis((AUClast) | Approximately 2 years | Area under concentration-time curve from time zero to the last measurable concentration for HMPL-A830 (antibody drug conjugate, total antibody and payload) |
| Pharmacokinetic Analysis((AUCtau) | Approximately 2 years | Area under concentration-time curve from time zero to the end of the dosing interval for HMPL-A830 (antibody drug conjugate, total antibody and payload) |
| Incidence of anti-drug antibodies (ADAs) against HMPL-A830 | Approximately 2 years | Number and percentage of patients developing anti-HMPL-A830 antibodies, and semiquantitative titer assessment. |
Countries
China
Outcome results
None listed