A Phase I Clinical Study of HMPL-A83 in Patients With Advanced Malignant Neoplasm

A Phase I, Multicenter, Open-label Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-A83 in Patients With Advanced Malignant Neoplasm

This is an open-label, first-in-human (FIH) Phase I study to evaluate the safety, tolerability, and preliminary efficacy of a humanized anti-CD47 monoclonal antibody (HMPL-A83) in patients with advanced malignant neoplasm.

Study Overview

• Status: Completed
• Conditions: Advanced Tumors
• Intervention / Treatment: Drug: HMPL-A83 injection

Detailed Description

This is an open-label, first-in-human (FIH) Phase I study to evaluate the safety, tolerability, and preliminary efficacy of a humanized anti-CD47 monoclonal antibody (HMPL-A83) in patients with advanced malignant neoplasm. The sample size of this study is mainly based on the design of classical 3 + 3 combined accelerated titration dose escalation with a total of 6 dose groups, and approximately 31-84 patients are expected to be enrolled. During the dose escalation, DLT-nonevaluable patients will be replaced, or the actual number of patients enrolled may exceed the planned one due to adjustment of escalation schedule during the dose escalation. It is expected that no more than 99 patients will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
  • Jinan
    • Shandong, Jinan, China
      • Shandong Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Orient Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Solid tumors/lymphomas/AML/MDS with confirmed per study protocol;
2. Is willing and able to provide informed consent;
3. Aged 18-75 years (inclusive);
4. Life expectancy ≥12 weeks as judged by the investigator;
5. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception per study protocol.

Exclusion Criteria:

1. Previous exposure to any agent targeting the CD47/SIRP alpha axis.
2. Those concurrently participating in another interventional clinical study, excluding those concurrently participating in an observational (non-interventional) clinical study, or in the survival follow-up phase of an interventional study.
3. Those have received any investigational drug within 4 weeks prior to the first dose of study drug (note: investigational drug refers to the drug that has not been approved for marketing in China).
4. Those with prior anti-tumor therapy-induced toxicity (excluding alopecia or fatigue) not recovered to Grade 0 or 1 as defined by NCI CTCAE v5.0, including immune-related adverse events (irAEs) that have not recovered following immunotherapy, prior to the first dose of study treatment (≥ 4 weeks);
5. Those expected to require other systemic anti-tumor therapies such as chemotherapy, immunotherapy, biotherapy, or hormonal therapy (except palliative radiotherapy) during the study.
6. Those who have received prior immunotherapy such as anti-PD- (L) 1 antibody and discontinued due to ≥ Grade 3 irAEs.
7. Those with known hereditary or acquired bleeding disorder; uncontrolled active bleeding, coagulopathy; prior history of chronic haemolytic anaemia or positive hemolysis test at screening.
8. Patients with a history of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolism within two years prior to enrollment, or those currently requiring anticoagulant or thrombolytic therapy as a therapeutic use.
9. Those have received immunosuppressive drugs within 4 weeks prior to the first dose of study drug
10. Those requiring long-term systemic hormonal therapy or any other immunosuppressive medication (excluding inhaled corticosteroid therapy or treatment at equivalent physiological doses).
11. Those have received live attenuated vaccines within 4 weeks prior to the first dose of study drug or planned to receive live attenuated vaccines during the study (for solid tumors)/any type of vaccine (for lymphoma, AML, MDS).
12. Those who have received any major surgical operation or uncured wound, ulcer or bone fracture within 4 weeks prior to the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HMPL-A83; Drug: HMPL-A83 The starting dose of HMPL-A83 is 0.3 mg/kg IV QW with escalating dose levels of 1, 3, 10, 20, and 30 mg/kg IV QW, in 28-day treatment cycles. During the study, the below dose had also been selected: 10,20, and 30 mg/kg Q2W in 28-day treatment cycles; 30 and 45mg/kg Q3W.	Drug: HMPL-A83 injection; Day 1,8,15,22 dose; 28 day treatment cycles.; Other Names: HMPL-A83

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety information/AE,SAE	To evaluate the safety and tolerability of HMPL-A83 in patients with advanced tumors	up to 3 years
MTD and RP2D	To determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of HMPL-A83 in patients with advanced tumors.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK endpoints	To investigate the pharmacokinetic (PK) profile of HMPL-A83 in patients with advanced tumors, including but not limited to the maximum plasma concentration (Cmax), trough concentration (Ctrough or Cmin), elimination half-life (t1/2), area under the plasma concentration-time curve (AUC0-t, AUC0-∞, AUC0-τ), apparent clearance (CL), apparent volume of distribution at steady state (Vss), etc.	up to 3 years
Efficacy endpoints	objective response rate (ORR)	up to 3 years

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Ye Guo, Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): April 7, 2025

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CD47, HMPL-A83
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2021-A83-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No