Clinical trial NCT05429008: A Phase I Clinical Study of HMPL-A83 in Patients With Advanced Malignant Neoplasm
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Tumors
Keywords: CD47, HMPL-A83
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-06-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: safety information/AE,SAE
timeFrame: up to 3 years
measure: MTD and RP2D
timeFrame: up to 2 years
Secondary outcomes:
measure: PK endpoints
timeFrame: up to 3 years
measure: Efficacy endpoints
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shandong
country: China
facility: Shandong Cancer Hospital
state: Jinan
city: Shanghai
country: China
facility: Shanghai Orient Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Ye Guo
role: PRINCIPAL_INVESTIGATOR
References: