WTX212A Monotherapy and in Combination With PD -1/PD-L1 Monoclonal Antibody

A Single-center, Open Label, Exploratory Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of WTX212A Injection Combined With PD -1/PD-L1 Monoclonal Antibody in Patients With Advanced Lung Cancer

This trial is a single-center, open-label designed investigator-initiated clinical study (IIT) to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of WTX212A injection WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in patients with advanced lung cancer

Study Overview

• Status: Recruiting
• Conditions: Advanced Lung Cancer
• Intervention / Treatment: Drug: WTX212A injection; Drug: PD -1/PD-L1 monoclonal antibody

Detailed Description

The trial consist of Screening Period (30 days), Treatment Period (21*n days), Safety Follow-up Period (90 days) and Survival follow-up.

About 20 subjects are planned to be enrolled in the study.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: pingli wang, phD; Phone Number: (0571)87783520; Email: pingliwang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Pingli Wang, M.D; Phone Number: +86 135 1680 8409; Email: pingliwang@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subject signs an informed consent form, understands this study, is willing to follow and has the ability to complete all experimental procedures;
• Regardless of gender, aged 18 to 75 years old (including threshold);
• Histologically or cytologically confirmed locally advanced (stage IIB/IIC) or metastatic (stage IV) non-small cell lung cancer (NSCLC) with disease progression or intolerance after treatment or extensive stage small cell Lung cancer (SCLC)
• Patients with lung cancer who have been treated with at least 1 line system therapy or cannot currently receive standard therapy, and who have been treated with PD-1 or PD-L1 inhibitor antibody in the terminal line therapy regimen for ≥ 2 cycles;
• ECOG ≤1
• Expected life ≥ 3 months；
• 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;

Exclusion Criteria:

• 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,
• Patients with clinical symptoms and the need for repeated drainage of pleural and ascitic fluids;
• Previous or recent history of pulmonary fibrosis, severe lung function damage caused by pneumoconiosis, radiation pneumonia, and drug-related pneumonia;
• There have been adverse events related to the use of IO drugs that require permanent cessation of IO treatment;
• Known to have other malignant tumors, currently progressing or completing treatment at least once in the past 3 years. Exceptions include early tumors that have received radical treatment (carcinoma in situ or grade 1 tumor, non ulcerative primary melanoma with a depth of less than 1mm and no lymph nodes involved), skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, or breast carcinoma in situ that has received potential radical treatment;
• 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;
• 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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed-dose in patients with advanced lung cancer; WTX212A injection Fixed-dose in advanced lung cancer patients	Drug: WTX212A injection; The WTX212A infusion is given every 21 days; Other Names: autologous red blood cell PD-1 inhibitor conjugate
Experimental: Combined Study in patients with advanced lung cancer; Fixed-dose WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in patients with advanced lung cancer	Drug: WTX212A injection; The WTX212A infusion is given every 21 days; Other Names: autologous red blood cell PD-1 inhibitor conjugate; Drug: PD -1/PD-L1 monoclonal antibody; The PD -1/PD-L1 monoclonal antibody is given every 21 days; Other Names: PD -1/PD-L1antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in the treatment of patients with IO- resistant advanced lung cancer.	Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the safety of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in the treatment of IO- resistant advanced lung cancer patients	The incidence of adverse events (AE), treatment related adverse events (TRAE), and severe adverse events (SAE) during the treatment of WTX212A injection	1 year
To evaluate the pharmacokinetic ( PK ) characteristics of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in patients with IO- resistant advanced lung cancer	Peak Plasma Concentration (Cmax)	1 year
To evaluate the immunogenicity of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in patients with IO -resistant advanced lung cancercheckpoint inhibitor resistance in advanced lung cancer patients	Describe the percentage of anti-drug antibodies (ADA) produced by subjects at each time point after treatment	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the pharmacodynamics ( PD ) characteristics of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in patients with IO- resistant advanced lung cancer	The occupancy rate of PD-1 receptor on the surface of peripheral blood T cells in subjects after WTX212A infusion	1 year
To explore and evaluate WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in the treatment of IO- resistant advanced lung cancer before and after treatment, analysis of immune cell subpopulations	Calculate the absolute values and percentages of immune cell subpopulations (absolute values and percentages of effector cells and immunosuppressive cells) before and after treatment of WTX212A injection combined with PD -1/PD-L1 monoclonal antibody in the treatment of IO -resistant advanced lung cancer. Immunomic analysis Variety	1 year
To explore and evaluate the changes in spleen size in patients with IO- resistant advanced lung cancer before and after treatment with WTX212A injection combined with PD -1/PD-L1 monoclonal antibody	Changes in spleen size before and after treatmen	1 year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Westlake Therapeutics
• Investigators: Principal Investigator: pingli wang, phD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immune Checkpoint Inhibitors
• Other Study ID Numbers: Reboot-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no plans to disclose the data

Drug and device information, study documents

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