TSN222 in Subjects With Advanced Solid Tumors or Lymphomas

NCT05842785 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TSN222-101CH
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a first-in-human \[FIH\], open-label phase 1/2 study of TSN222 in subjects with advanced solid tumors or lymphomas. This study is comprised of a Phase 1 dose escalation and Phase 2 dose expansion component.

Conditions

Has a Pathologically Documented Unresectable Locally Advanced or Metastatic Solid Tumor or Lymphoma

Outcome Measures

Primary Outcomes (3)

• Phase I-Safety

  A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with DYP688. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. AEs as characterized by nature, frequency, and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Secondary safety endpoint. The abnormal findings of vital sign, physical examination, laboratory measurements, ECG and ECHO/ MUGA parameters.

  28 days

• Phase I and phase II-Safety

  AEs as characterized by nature, frequency, and severity according to NCI CTCAE version 5.0.

  Any AEs (including SAEs) that occurs after first dose through 28 days after receiving the last dose of TSN222

• Phase II

  ORR based on investigator assessment using RECIST v 1.1 for solid tumor or Lugano 2014 response criteria for lymphomas.

  baseline and throughout the study

Secondary Outcomes (2)

• Phase I/II: PK profile

  From Cycle 1 to the first day of Cycle 2

• Phase I/II: To evaluate the preliminary anti-tumor activity of TSN222

  Durting the period of patient treatment

Study Arms (4)

Phase I Dose escalation

EXPERIMENTAL

100 microgram (μg), 200 μg, 400 μg, 800 μg, 1600 μg, and 3200 μg of TSN222 as a single agent in subjects with advanced solid tumors or lymphomas.

Drug: Phase I dose escalation

Phase II-HNSCC

EXPERIMENTAL

Patients with advanced squamous cell carcinoma of head and neck (HNSCC).

Drug: Phase II-HNSCC

Phase II-Advanced melanoma

EXPERIMENTAL

patients with the advanced melanoma.

Drug: Phase II-Advanced melanoma

Phase II-solid tumors or lymphomas.

EXPERIMENTAL

patients with advanced other types of solid tumors or lymphomas.

Drug: Phase II-solid tumors or lymphomas

Interventions

Phase I dose escalation DRUG

The eligible subjects will receive TSN222 via intratumoral (i.t.) injection on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Phase I Dose escalation

Phase II-HNSCC DRUG

The eligible subjects will receive RP2D of TSN222 via intratumoral (i.t.) injection on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Phase II-HNSCC

Phase II-Advanced melanoma DRUG

The eligible subjects will receive RP2D of TSN222 via intratumoral (i.t.) injection on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Phase II-Advanced melanoma

Phase II-solid tumors or lymphomas DRUG

The eligible subjects will receive RP2D of TSN222 via intratumoral (i.t.) injection on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Phase II-solid tumors or lymphomas.

Eligibility Criteria

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

You may qualify if:

• The subject fully understands the requirements of the study and voluntarily signs the ICF.
• At least 18 years of age at the time of informed consent.
• Life expectancy of 3 months or more.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Willing to provide tumor tissues and accept tumor biopsies during study.
• At least one measurable tumor lesion per RECIST v1.1 or Lugano 2014 response criteria (only applicable for phase 2); note: the measurable lesions should be non-injected and non-biopsied during study.
• Subjects must meet the following criteria for each of the respective parts of the study
• Phase 1 part:
• Has a pathologically documented unresectable locally advanced or metastatic solid tumor or lymphoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• Phase 2 part:
• Cohort 1: Has pathologically confirmed diagnosis of unresectable locally advanced or metastatic HNSCC that is considered incurable by local therapies, and is refractory to or intolerable with at least one systemic treatment in the advanced setting.
• Cohort 2: Has pathologically confirmed diagnosis of unresectable locally advanced or metastatic melanoma that is refractory to or intolerable with at least prior two systemic treatments in the advanced setting for BRAF mutant subjects, or at least one systemic treatment in the advanced setting for BRAF non-mutant subjects.
• Cohort 3: Has pathologically confirmed diagnosis of unresectable locally advanced or metastatic other solid tumors or lymphomas that is refractory to or intolerable with at least one systemic treatment in the advanced setting, or for which no standard treatment is available.
• \. Adequate bone marrow function: 10. Adequate renal function: estimated creatinine clearance ≥ 50 mL/min as calculated using Cockcroft-Gault formula.
• \. Adequate liver function: 12. Blood albumin ≥ 30g/L. 13. Adequate coagulation function: 14. Women of childbearing potential (WOCBP) and men must agree to follow instructions for method(s) of contraception during the treatment period and for at least 6 months after the last dose of TNS222. Contraception methods should be consistent with local regulations. Refer to Appendix 6 for details and definitions of WOCBP, postmenopausal females and contraception guidance.

You may not qualify if:

• Subjects will be excluded if they meet any of the following criteria:
• Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroid for at least 4 weeks following CNS directed therapy are eligible for study entry.
• Prior history of active malignant disease other than that being treated in this study. Exceptions: malignancies that were treated curatively and have not recurred within the past 5 years (i.e., completely resected basal cell carcinoma and squamous cell carcinoma of the skin; and completely resected carcinoma in situ of any type) (only applicable to phase 2 part).
• Any unresolved Grade 2 or higher toxicity from previous anticancer therapy except alopecia and grade 2 peripheral neuropathy.
• Prior systemic anti-cancer treatment (chemotherapy, biologic therapy, or targeted therapy or herbal medicine) within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug; or prior systemic anti-tumor immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
• Radical radiation within 4 weeks prior to the first dose of study drug; palliative radiotherapy to a non-target lesion within 2 weeks prior to the first dose of study drug.
• Has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to the first dose of study drug.
• Major surgery within 4 weeks prior to first dose of study drug.
• Severe infection within 4 weeks prior to the first dose of study drug, active infection requiring oral or intravenous antibiotics within 2 weeks prior to the first dose of study drug.
• Active viral hepatitis.
• History of human immunodeficiency virus (HIV) infection.
• Known interstitial lung disease history, or current active pneumonitis, radiation pneumonitis requiring hormonal therapy, or uncontrolled lung disease.
• Symptomatic uncontrolled effusion in body cavities (e.g., pleural effusion, ascites and pericardial effusion).
• History of significant bleeding event (\> 30ml) within 3 months before the first dosing or hemoptysis (\> 2.5 mL of bright red blood or at least 0.5 teaspoon per episode) within 4 weeks before the first dosing；
• Severe cardiovascular disease within 6 months of the first dose including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina, New York Heart Association (NYHA) class III or IV heart failure or uncontrolled arrhythmia.

Sponsors & Collaborators

• Tyligand Bioscience (Shanghai) Limited: lead

Study Sites (1)

Fudan Cancer Hospital

Shanghai, Shanghai Municipality, 200063, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Lymphoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Jian Zhang

  Fudan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tyligand Clinical Trial Info

CONTACT

8621-50720081; clinical_trial@tyligand.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Firstly conduct the phase I and find the RP2D. Once we have the RP2D, we will conduct the phase II study.

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 6, 2023
• Study Start: July 26, 2023
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 29, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)