A Phase 1/2 Study of TY101 for Locally Advanced /Metastatic Solid Tumors and Relapsed or Refractory Lymphomas

NCT04458389 | Unknown Phase 1 DMC

• 1 other identifier: TY101-001
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 3

Brief Summary

A multicenter, open-label, dose-escalation and dose-expansion phase 1/2 study, to evaluate TY101 safety, tolerability, pharmacokinetic characteristics, effectiveness and immunogenicity in patients with Locally Advanced /Metastatic Solid Tumors and Relapsed or Refractory Lymphomas. The study includes two parts: dose escalation and expansion cohort to evaluate the tolerability and efficacy.

Conditions

Locally Advanced /Metastatic Solid Tumors; Relapsed or Refractory Lymphomas

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability measured

  Number of Participants with treatment-related Adverse Events (AEs) by CTCAE v5.0.

  90 days after the last dose.

• Dose-limiting toxicity(DLT)

  DLT is the primary endpoint for safety in the dose escalation phase and will be used to determine the maximum tolerated dose (MTD).

  3 weeks after first dose for each dose group.

Secondary Outcomes (8)

• Pharmacokinetics(Cmax)

  Up to approximately 12 months

• Pharmacokinetics(Tmax)

  Up to approximately 12 months

• Pharmacokinetics(AUC)

  Up to approximately 12 months

• Pharmacokinetics(t1/2)

  Up to approximately 12 months

• Pharmacokinetics(PPK)

  The PPK evaluation will be further designed based on the results of the dose escalation phase.

Study Arms (1)

TY101

EXPERIMENTAL

Dose escalation：Humanized anti-PD-1 monoclonal antibody is to be injected intravenously 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg (fix dose) until disease progresses or unacceptable tolerability occurs. Dose expansion：After completion of the DLT observation, the sponsor and principal investigator will select a possible dose（RP2D）for dose expansion to further confirm the efficacy and safety of RP2D.

Drug: TY101

Interventions

TY101 DRUG

Dose escalation: TY101 0.3mg/kg or 1mg/kg or 3mg/kg or 10mg/kg 200mg Intravenous Q3W, 2 years depending on response. Dose expansion: Subjects received TY101 injection for a maximum of 2 years until progressive disease, intolerant toxicity, death, or withdrawal from the study occurred.

TY101

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years
• Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
• Histological or cytological diagnosis, advanced solid tumor and lymphoma(Dose escalation phase), Or recurrence and refractory peripheral T-cell lymphoma who must have failure at least 1 prior routine regimen, or failure to tolerate the toxicity, or lack of any routine regimens, advanced squamous cell carcinoma of the skin and other advanced solid tumors and lymphoma (Dose expansion phase）
• At least one evaluable lesion for solid tumor or lymphoma.
• Must provide with tumor specimen that meet the requirements for biomarker testing(expression of PD-L1 and the infiltrating lymphocytes).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the screening and without deterioration within 2 weeks before enrollment.
• Life expectancy ≥12 weeks
• Adequate organ function as evidenced by meeting all the following requirements (with 14 days):
• Hemoglobin ≥ 9.0 g/dL neutrophils ≥ 1500 cells/ µL platelets ≥ 100× 10\^3/ µL;
• Total bilirubin ≤ 1.5×upper limit of normal(ULN) aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5×ULN without, and ≤ 3×ULN with hepatic metastasis;
• International Normalized Ratio (INR) ≤1.5×ULN;
• Serum creatinine ≤1×ULN, creatinine clearance \>60ml/min (Cockcroft-Gault equation).
• The results of blood pregnancy tests must be negative for premenopausal women screened. All enrolled patients (male or female) should agree with adequate and reliable barrier contraception from signing informed consent date to the 6 months after the last dose.

You may not qualify if:

• Previously received any of the following therapies:
• Received any other cytotoxic chemotherapeutic agents within 4 weeks prior to the first dose; for nitrosoureas and mitomycin C at least 6 weeks.
• Received any targeted or other anticancer drug therapy within 4 weeks prior to the first dose.
• Radiation therapy within 4 weeks prior to first dose (note: palliative radiotherapy for bone or palliative radiotherapy for superficial lesions was allowed, the course of treatment is based on local standards and had been ended 2 weeks before the first dose. Radiotherapy covering more than 30% of the bone marrow area within 4 weeks prior to first dose was excluded).
• NMPA-approved antitumor Chinese traditional medicine is in use or has been used within 2 weeks prior to the first dose.
• Concurrent malignancy within 5 years prior to screening, except for the cured basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Patients with active central nervous system (CNS) metastasis and/or cancerous meningitis who were found on known or in the screening tests, except for the following subjects: Subjects with asymptomatic brain metastasis who need to undergo regular brain imaging examination as the site of the disease. Subjects with stable status of brain metastasis after treatment.
• Concomitant active or suspected autoimmune disease; but patients who are in a stable state and did not require systemic immunosuppressive therapy are allowed to be enrolled.
• A history of allogeneic organ, bone marrow transplant or stem cell transplant; A history of allogeneic organ, bone marrow or stem cell transplantation.
• Patients with the history of or are suffering from pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe pulmonary function impairment, etc., which may interfere with the detection and management of suspected drug-related pulmonary toxicity; patients with active tuberculosis or with a history of active tuberculosis infection ≤48 weeks prior to screening, regardless of treatment.
• Severe cardiovascular disease, such as NYHA class III or IV congestive heart failure. A history of myocardial infarction, poorly controlled arrhythmias (including QTc interphase ≥450 ms in men and ≥470 ms in women, as calculated by the Fridericia formula), or cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis, and pulmonary embolism in the 6 months prior to screening.
• Uncontrolled hypertension (systolic blood pressure \>150 mmHg and diastolic blood pressure \> 100 mmHg), a history of hypertension crisis, or a history of hypertensive encephalopathy.
• Uncontrolled endocrine diseases (diabetes, thyroid disease, etc.).
• Patients with active peptic ulcer or hemorrhagic disease.
• Seriously infected persons who need to be treated with systemic antiviral or antimicrobial treatment.

Sponsors & Collaborators

• Tayu Huaxia Biotech Medical Group Co., Ltd.: lead

Study Sites (3)

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, 100021, China

RECRUITING

The Fifth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, 100071, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Lymphoma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Guanwen Zeng, PhD

CONTACT

8610-85187670; kevintseng@tayubiotech.com

Study Design

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

Model Details: TY101 injection

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 7, 2020
• Study Start: December 7, 2020
• Primary Completion: June 30, 2024
• Study Completion: July 31, 2025
• Last Updated: August 13, 2021

Record last verified: 2021-05

Locations

CN (3)