Safety, Tolerability and Preliminary Efficacy of Erythrocyte-αPD-1 Conjugate in Patients With Advanced Malignancies

Safety, Tolerability and Preliminary Efficacy of Erythrocyte-αPD-1 Conjugate Injection in Patients With Advanced Malignancies

This is an investigator-initiated, multi-center, open-label clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of Erythrocyte-αPD-1 conjugates in patients with advanced malignancies

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer; Solid Tumor; Hematologic Malignancy
• Intervention / Treatment: Drug: Engineered erythrocytes (or red blood cells) covalently conjugated with commercially available anti-PD-1 antibodies on their membranes

Detailed Description

This is an investigator-initiated, multi-center, open-label clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of Erythrocyte-αPD-1 conjugates in patients with unresectable or metastatic advanced malignancies who have failed previous systemic therapy.

The study was divided into two phases: dose escalation and dose expansion

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Liu Yang, PhD; Phone Number: 0571-85893889; Email: yangliu@hmc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject signs an informed consent form, understands this study, is willing to follow and has the ability to complete all experimental procedures;
2. Regardless of gender, aged 18 to 75 years old (including threshold);
3. Patients with advanced malignant tumors who have been confirmed by histopathology;
4. Patients with histopathologically confirmed unresectable or metastatic solid tumors who have failed systemic treatment or have no effective standard treatment, or who are unwilling to accept standard treatment or are not suitable for standard treatment;
5. ECOG≤1；
6. Expected life ≥ 3 months；
7. Male participants, their spouses, and female participants of childbearing age should agree to use a medically recognized effective contraceptive method from the signing of the informed consent form until 3 months after the last administration; Pregnancy testing results for women of childbearing age within ≤ 7 days before the first trial drug administration must be negative. Women of childbearing age include premenopausal women and women within 2 years after menopause.

Exclusion Criteria:

1. People with other serious medical diseases, including but not limited to: uncontrolled diabetes, active peptic ulcer, active bleeding, etc., and people with uncontrollable or serious cardiovascular diseases,
2. Patients with clinical symptoms and the need for repeated drainage of pleural and ascitic fluids;
3. Previous or recent history of pulmonary fibrosis, severe lung function damage caused by pneumoconiosis, radiation pneumonia, and drug-related pneumonia;
4. There have been adverse events related to the use of IO drugs that require permanent cessation of IO treatment;
5. Known to have other malignant tumors, currently progressing or completing treatment at least once in the past 3 years.
6. Subjects with symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination and clinically unstable for at least 14 days prior to enrollment who require steroid treatment;
7. Having hereditary bleeding tendencies or coagulation disorders, or a history of thrombosis, hemolysis, or hemorrhagic diseases; Received significant surgical treatment or obvious traumatic injury within 28 days prior to the start of research treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Dose Escalation of Erythrocyte-αPD-1 conjugate monotherapy in patients with advanced malignancy	Drug: Engineered erythrocytes (or red blood cells) covalently conjugated with commercially available anti-PD-1 antibodies on their membranes; Engineered erythrocytes (or red blood cells) covalently conjugated with commercially available anti-PD-1 antibodies on their membranes
Experimental: Dose Expansion; Dose Expansion of Erythrocyte-αPD-1 conjugate monotherapy in patients with advanced malignancy	Drug: Engineered erythrocytes (or red blood cells) covalently conjugated with commercially available anti-PD-1 antibodies on their membranes; Engineered erythrocytes (or red blood cells) covalently conjugated with commercially available anti-PD-1 antibodies on their membranes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	The incidence of adverse events (AE), treatment related adverse events (TRAE), and severe adverse events (SAE) during the treatment of engineered erythrocytes	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics characteristics Peak Plasma Concentration(Cmax)	The occupancy rate of PD-1 receptor on the surface of peripheral blood T cells in subjects after infusion,including Peak Plasma Concentration(Cmax)	through study completion, an average of 1 year
Pharmacodynamics characteristics Area under the plasma concentration versus time curve（AUC）	The occupancy rate of PD-1 receptor on the surface of peripheral blood T cells in subjects after infusion,including Area under the plasma concentration versus time curve (AUC).	through study completion, an average of 1 year
Efficacy of Erythrocyte-αPD-1 Conjugate	According to RECIST 1.1, the effectiveness of Erythrocyte-αPD-1 Conjugate injection in the treatment of patients with unresectable or metastatic advanced solid tumors was evaluated. The evaluation indicators included objective response rate (ORR),etc.	per 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibody (ADA)	Describe the number of anti-drug antibodies (ADA) produced by subjects at each time point after treatment.	through study completion, an average of 1 year
Peripheral immune response assessment	Immune cell alterations(number of T-cell,etc) in the peripheral are analyzed by flow cytometry.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Zhejiang Provincial People's Hospital
• Collaborators: Westlake Therapeutics
• Investigators: Principal Investigator: Yang Liu, PhD, ZHEJIANG PROVINCIAL PEOPLE'S HOSPITAL of China

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Solid Tumor; Hematologic Malignancy
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: WTX212-002CN

Drug and device information, study documents

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