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

Phase 1

Recruiting

• Conditions: Advanced Tumors
• Interventions: Drug: HMPL-A83 injection

• Registration Number: NCT05429008
• Lead Sponsor: Hutchmed

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-06-14
• Study First Submitted QC: 2022-06-17
• Study First Posted: 2022-06-23
• Study Start: 2022-07-15
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06
• Primary Completion: 2025-06-07
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 99

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HMPL-A83	HMPL-A83 injection	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
PK endpoints	up to 3 years	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.
Efficacy endpoints	up to 3 years	objective response rate (ORR)

Trial Locations

Locations (3)

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Shandong Cancer Hospital; 🇨🇳 Shandong, Jinan, China

Shanghai Orient Hospital; 🇨🇳 Shanghai, Shanghai, China