Evaluating TY101 for advanced solid tumors and lymphomas

Phase 1 (Dose Escalation)/Phase 2 (Expansion Cohort) Trial of TY101 as a Single Agent in Patients With Locally Advanced/Metastatic Solid Tumors and Relapsed or Refractory Lymphomas

This study is testing a new treatment called TY101 to see if it can safely help people with advanced solid tumors and certain types of lymphomas.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 268 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tayu Huaxia Biotech Medical Group Co., Ltd. (industry)
• Drugs / interventions: Radiation
• Locations: 3 sites (Beijing, Beijing and 2 other locations)
• Trial ID: NCT04458389 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, dose-escalation and dose-expansion study designed to assess the safety, tolerability, pharmacokinetics, effectiveness, and immunogenicity of TY101 in patients with locally advanced or metastatic solid tumors and relapsed or refractory lymphomas. The study consists of two parts: an initial dose escalation phase to determine the maximum tolerated dose, followed by an expansion cohort to further evaluate efficacy and safety. Participants will be closely monitored for treatment responses and side effects throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors or relapsed/refractory lymphomas who have not responded to previous treatments.

Not a fit: Patients with early-stage cancers or those who have not yet undergone any treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors and lymphomas that are difficult to treat.

How similar studies have performed: Other studies have shown promise with similar immunotherapeutic approaches, suggesting potential for success in this area.

Eligibility criteria

Inclusion Criteria:

1. Male or female ≥18 years
2. 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.
3. 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）
4. At least one evaluable lesion for solid tumor or lymphoma.
5. Must provide with tumor specimen that meet the requirements for biomarker testing(expression of PD-L1 and the infiltrating lymphocytes).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the screening and without deterioration within 2 weeks before enrollment.
7. Life expectancy ≥12 weeks
8. Adequate organ function as evidenced by meeting all the following requirements (with 14 days):

   1. Hemoglobin ≥ 9.0 g/dL neutrophils ≥ 1500 cells/ µL platelets ≥ 100× 10\^3/ µL;
   2. 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;
   3. International Normalized Ratio (INR) ≤1.5×ULN;
   4. Serum creatinine ≤1×ULN, creatinine clearance \>60ml/min (Cockcroft-Gault equation).
9. 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.

Exclusion Criteria:

1. Previously received any of the following therapies:

   1.1 Received any other cytotoxic chemotherapeutic agents within 4 weeks prior to the first dose; for nitrosoureas and mitomycin C at least 6 weeks.

   1.2 Received any targeted or other anticancer drug therapy within 4 weeks prior to the first dose.

   1.3 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).

   1.4 NMPA-approved antitumor Chinese traditional medicine is in use or has been used within 2 weeks prior to the first dose.
2. 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.
3. 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.
4. 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.
5. A history of allogeneic organ, bone marrow transplant or stem cell transplant; A history of allogeneic organ, bone marrow or stem cell transplantation.
6. 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.
7. 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.
8. Uncontrolled hypertension (systolic blood pressure \>150 mmHg and diastolic blood pressure \> 100 mmHg), a history of hypertension crisis, or a history of hypertensive encephalopathy.
9. Uncontrolled endocrine diseases (diabetes, thyroid disease, etc.).
10. Patients with active peptic ulcer or hemorrhagic disease.
11. Seriously infected persons who need to be treated with systemic antiviral or antimicrobial treatment.
12. Pericardial effusion, pleural effusion and peritoneal effusion that remained uncontrolled after intervention.
13. Patients with any other severe, acute or chronic disease that the investigator considers to be likely to interfere with participation in the study or evaluation and which the investigator determines to be inappropriate for participation in the clinical trial.
14. HIV infection.
15. Active viral hepatitis patients are excluded. Patients with serologic evidence of chronic HBV infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test, and the HBV-DNA); HCV infection (defined by positive HCV antibody and HCV-RNA test).
16. The history of other therapies against immune checkpoint, such as anti-PD-1, anti-PD-L1, anti-CTLA-4 or anti-LAG-3.
17. Have received steroids or other systemic immunosuppressive therapy within 14 days prior to the first dose, or have to be treated while on trial; except the following: a) The use of topical or inhaled corticosteroids, b) Glucocorticoids are used in the short term (continuous use≤7 days) to prevent or treat non-autoimmune allergic diseases.
18. History of serious allergic reaction to treatment with another monoclonal antibody.
19. A history of alcohol, drug or substance abuse.
20. Major surgery within 4 weeks prior to screening or scheduled to undergo major surgery during the trial.
21. Live virus vaccine or attenuated vaccine within 30 days prior to first dose.
22. Be in the other clinical studies now, or have participated in other intervention clinical trials in the previous 4 weeks.
23. Pregnant or breast-feeding females.
24. Any condition that the investigator believes may not be appropriate for participating the study.

Where this trial is running

Beijing, Beijing and 2 other locations

• Cancer Hospital Chinese Academy of Medical Science — Beijing, Beijing, China (RECRUITING)
• The Fifth Medical Center of PLA General Hospital — Beijing, Beijing, China (RECRUITING)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (RECRUITING)

Study contacts

• Study coordinator: Guanwen Zeng, PhD

Conditions: Locally Advanced /Metastatic Solid Tumors, Relapsed or Refractory Lymphomas