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

Advanced Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05429008
• Other study ID #: 2021-A83-00CH1
• Status: Recruiting
• Phase: Phase 1
• Start date: July 15, 2022
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: Hutchmed
• Contact: Haiying Hong, CPM
• Phone: 17317300326
• Email: haiyingh[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: September 2025
• Est. primary completion date: June 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Tumors
• Neoplasms

Intervention

Drug:
• HMPL-A83 injection
Day 1,8,15,22 dose; 28 day treatment cycles.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Shandong Cancer Hospital	Shandong	Jinan
China	Shanghai Orient Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Hutchmed

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety information/AE,SAE	To evaluate the safety and tolerability of HMPL-A83 in patients with advanced tumors	up to 3 years
Primary	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	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, AUC0-8, AUC0-t), apparent clearance (CL), apparent volume of distribution at steady state (Vss), etc.	up to 3 years
Secondary	Efficacy endpoints	objective response rate (ORR)	up to 3 years