A Trial of Y101D, a PD-L1/TGF-β Bispecific Antibody, in Patients With Metastatic or Locally Advanced Solid Tumors

NCT05028556 | Completed Phase 1

• 1 other identifier: Y101D01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase 1, multicenter, open-label study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of Y101D in patients with metastatic or locally advanced solid tumors.

Conditions

Metastatic or Locally Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLTs)

  DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0.

  From the time of the first dose (Day 1) until the 2nd dosing (Day 28)

• Adverse Events according to CTCAE V5.0

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Time Frame: From the start of administration to the end of the study or 28 days after the administration is stopped (up to 6 months and 28 days)

Secondary Outcomes (10)

• Area under the curve (AUC) of Y101D

  Up to 1 weeks after the 2nd dosing

• Peak Plasma Concentration (Cmax) of Y101D

  Up to 1 weeks after the 2nd dosing

• Half-time (t1/2) of Y101D

  Up to 1 weeks after the 2nd dosing

• immunogenicity

  From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).

• Objective Response Rate (ORR)

  6 months (anticipated)

Study Arms (1)

Y101D

EXPERIMENTAL

Y101D in subjects with Metastatic or Locally Advanced Solid Tumors

Drug: Cohort 1 of Y101D; Drug: Cohort 2 of Y101D; Drug: Cohort 3 of Y101D; Drug: Cohort 4 of Y101D; Drug: Cohort 5 of Y101D

Interventions

Cohort 1 of Y101D DRUG

Y101D, 1mg/kg, Q2W, intravenous infusion

Y101D

Cohort 2 of Y101D DRUG

Y101D, 3mg/kg, Q2W, intravenous infusion

Y101D

Cohort 3 of Y101D DRUG

Y101D, 10mg/kg, Q2W, intravenous infusion

Y101D

Cohort 4 of Y101D DRUG

Y101D, 20mg/kg, Q2W, intravenous infusion

Y101D

Cohort 5 of Y101D DRUG

Y101D, 30mg/kg, Q2W, intravenous infusion

Y101D

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18\~75 (including 18 and 75 years old), gender is not limited;
• Pathologically confirmed metastatic or locally advanced solid tumors with failure or absence of standard care;
• ECOG physical status score must be 0\~1;
• Expected survival of subjects evaluated by the investigator ≥3 months;
• Hemogram: absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin ≥90g/L (no red blood cells were injected within 14 days before the first administration), platelet ≥90×109/L;
• Liver: bilirubin ≤1.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal value;If the subject has liver metastasis, ALT and AST are allowed to be less than 5 times the upper limit of normal value;
• Kidney: Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance ≥ 60 mL/min (using standard Cockcroft-Gault formula);
• Understand and voluntarily sign written informed consent.

You may not qualify if:

• Have received chemotherapy, radiotherapy (local palliative radiotherapy for 14 days) and immunotherapy within 28 days before the first administration, and have received small molecule targeted drugs or Chinese patent drugs with anti-tumor indications within 14 days;
• Major surgery (except diagnostic biopsy) within 28 days prior to the first dose;
• Subjects with central nervous system (CNS) metastases causing clinical symptoms or requiring therapeutic intervention;Patients who had previously received BMs were included if they were asymptomatic ≥4 weeks prior to initial dosing, had stable disease on radiographic findings, and did not require corticosteroid or anticonvulsant therapy;
• Receive any organ transplantation, including allogeneic stem cell transplantation, except those that do not require immunosuppression (e.g. cornea transplantation, hair transplantation);
• Adverse events caused by previous antitumor therapy have not recovered (i.e., grade 1 or at baseline), except for hair loss and grade 2 neuropathy, hormone replacement hypothyroidism, or other confirmed chronic adverse events;
• Subjects with a history of malignancy (non-study tumor) within 3 years prior to the first study administration date (other than skin squamous cell carcinoma and basal cell carcinoma, carcinoma in situ of the cervix or breast, or other non-invasive lesions that the Investigator and Sponsor agree have been cured and have a very low risk of recurrence within 3 years);
• Have a known allergy, hypersensitivity or intolerance to corticosteroids, monoclonal antibodies or human proteins or their excipients;
• Uncontrolled active infection (CTCAE≥2);
• Subjects with a history of serious cardiovascular disease, including previous coronary artery bypass grafting or stent implantation, myocardial infarction or cerebrovascular accident within 6 months, history of congestive heart failure or unstable angina pectoris, uncontrolled severe hypertension, and arrhythmias requiring medication;
• Active autoimmune diseases (such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus (sle), hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, etc.), into the group when the disease is in stable except ZhuangTaiZhe (no need to systemic immune inhibitors to treat symptoms stable under the condition of more than 6 months).
• Subjects with uncontrolled metabolic diseases such as diabetes, severe gastrointestinal bleeding, and severe diarrhea (CTCAE≥2), and subjects with severe gastrointestinal obstruction requiring intervention;
• Human immunodeficiency virus (HIV) antibody positive, hepatitis B virus (HBV) surface antigen positive and HBV DNA test indicated active hepatitis B (HBV-DNA≥1000cps/ml), active hepatitis C (hepatitis C antibody positive and HCV-RNA higher than the detection limit of the analysis method), active syphilis;
• Those who received live (attenuated) virus vaccine within 4 weeks before the first administration;
• Pregnant or lactating women or men or women who have a birth plan within 12 months;
• Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia;

Sponsors & Collaborators

• Wuhan YZY Biopharma Co., Ltd.: lead

Study Sites (3)

Cancer Prevention Center, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Li Zhang, MD

  Cancer Prevention Center, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 31, 2021
• Study Start: August 6, 2021
• Primary Completion: July 5, 2024
• Study Completion: September 9, 2024
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)