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.
Phase 1 Part: Using the standard 3+3 design for dose escalation, the Phase 1 Part will evaluate the prespecified 6 sequential dose levels of 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. The eligible subjects will receive TSN222 via i.t. injection on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity. The dose-limiting toxicity (DLT) observation period will be defined as the first 28 days after the first dose (i.e. the first cycle). Based on the standard "3+3" design, cohorts of 3 to 6 subjects each will be sequentially assigned to the predefined dose levels. Dose escalation will continue until up to the highest planned dose or the MTD or RP2D is determined. Phase 2 Part: Phase 2 part will evaluate the efficacy and safety of TSN222 as monotherapy at the preliminary RP2D(s) in 3 cohorts bellow: Cohort 1: advanced squamous cell carcinoma of head and neck (HNSCC). Cohort 2: advanced melanoma. Cohort 3: advanced other types of solid tumors or lymphomas.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
162
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.
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.
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.
Fudan Cancer Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGPhase 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.
Time frame: 28 days
Phase I and phase II-Safety
AEs as characterized by nature, frequency, and severity according to NCI CTCAE version 5.0.
Time frame: 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.
Time frame: baseline and throughout the study
Phase I/II: PK profile
Plasma concentrations and PK parameters of TSN222 and its metabolites including but not limited to area under the plasma concentration-time curve (AUC), maximum concentrations (Cmax), trough concentrations (Ctrough).
Time frame: From Cycle 1 to the first day of Cycle 2
Phase I/II: To evaluate the preliminary anti-tumor activity of TSN222
Based on investigators assessment: Overall response rate (ORR). Duration of response (DOR). Time to response (TTR). Disease control rate (DCR). Progression free survival (PFS).
Time frame: Durting the period of patient treatment
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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.