A Phase I/II Dose Escalation and Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of TJ011133 in Combination With Toripalimab in Subjects With Advanced Solid Tumors

TJ Biopharma Co., Ltd.22 sites in 1 country7 target enrollmentDecember 30, 2021

ConditionsAdvanced Solid Tumor

InterventionsTJ1133 Injection

DrugsTJ1133 Injection

Overview

Phase: Phase 1
Intervention: TJ1133 Injection
Conditions: Advanced Solid Tumor
Sponsor: TJ Biopharma Co., Ltd.
Enrollment: 7
Locations: 22
Primary Endpoint: The Objective Response Rate(ORR)
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a phase I/II study of single drug TJ011133 and Toripalimab combine treatment forAdvanced solid tumor. This study include two stages. First stage is dose escalation and second stage is dose extension. The purpose of part A is to comfirm the MTD or MED and the clinical dose. The purpose of part B is to observe the safty, effectiveness, PK, PD and biomarker properties for effective subjects.

Detailed Description

This is an open-label, multi-center phase I/II clinical trial which will enroll 96 to 102 subjects with advanced solid tumors. This study consists of two phases, the first of which is the dose escalation study of TJ011133 in combination with toripalimab, and the second stage is a dose expansion study. In phase 1, approximately 3 to 6 subjects will be enrolled in each group to receive TJ011133 (30 mg/kg, 45 mg/kg, QW) in combination with toripalimab injection (240 mg, Q3W). A safety assessment committee, consisting of the sponsor and the investigator, will assess the safety of the first 3 subjects at day 21 after the first dose to determine the safety of the doses as well as to determine whether to enroll 3 additional patients to continue to evaluate the safety. In the dose expansion phase, patients with melanoma, gastric cancer, and head and neck squamous cell carcinoma will be enrolled, with 30 patients for each malignancy, with a total of 90 patients. TJ011133 will be administered at a prespecified dose of 30 mg/kg or 45 mg/kg, QW or at a less frequency of Q2W or Q3W, and the dosing regimen will be determined based on the safety data obtained by PK/PD model analysis from other TJ011133 clinical studies. And TJ011133 will be given in combination with toripalimab injection at 240 mg, Q3W, until the occurrence of endpoint events such as intolerance or progressive disease.

Registry

clinicaltrials.gov

Start Date

December 30, 2021

End Date

February 3, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

TJ Biopharma Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female subjects aged ≥18 years old (inclusive);
•ECOG score: 0-1 points;
•Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors, and those who failed or were intolerant to standard therapy, or have no effective treatment options:
•Enrollment of patients with advanced solid tumors in the dose escalation phase;
•Subjects with melanoma, gastric cancer, head and neck squamous cell carcinoma will be enrolled in the dose expansion phase;
•Collect FFPE tumor tissue slides: Collect 12 to 13 archival pre-treatment (mandatory) and 10 on-treatment (optional) paraffin sections from fresh tumor biopsies.
•Subjects with at least 1 measurable lesion as per RECIST V1.1;
•Expected survival ≥ 3 months;
•Main organ function is normal (within 7 days prior to the first dose), i.e., relevant laboratory test criteria are met, and some laboratory indicators meet the following criteria:
•a) Hematology: i. Hemoglobin ≥ 11.0 g/dL or 6.8 mmol/L, received no blood transfusion within 7 days of evaluation, and without dependence on erythropoietin (EPO), ii. Absolute neutrophil count (ANC) ≥1.5×109/L, iii. Platelets ≥ 75×109/L; b) Renal function: i. Creatinine clearance ≥ 45 mL/min (calculated by Cockcroft-Gault formula), ii. Qualitative urine protein ≤ 1+; or qualitative urine protein ≥ 2+, 24-hour urine protein \< 1 g; c) Liver function i. Serum total bilirubin ≤ 1.5 × ULN, ii. Both aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 2.5 × ULN, iii. Serum albumin ≥ 2.8 g/dL (received no albumin infusion within 2 weeks prior to blood collection); d) Coagulation function: i. International normalized ratio (INR), or prothrombin time (PT) ≤ 1.5 x ULN, or PT parameters can be maintained ≤ 1.5 x ULN with an anticoagulant at a stable dose, ii. Activated partial thrombin time (aPTT) ≤ 1.5 × ULN, or aPTT parameters can be maintained ≤ 1.5 × ULN with the use of anticoagulants;

Exclusion Criteria

•Pregnant or breast-feeding women;
•Prior treatment with CD47 or SIRPα inhibitors;
•Prior CAR-T cell therapy;
•Subjects who have received systemic anti-tumor therapies within 4 weeks prior to the initiation of treatment or within five half-lives (whichever is shorter) of the study drug, except for the following;
•Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study drug;
•Oral fluorouracils and small molecule targeted agents are within 2 weeks prior to the first dose of study drug or within 5 half-lives of the drug, whichever is longer;
•Traditional Chinese medicine with anti-tumor indications is within 2 weeks prior to the first dose of study drug.
•Subjects who had or have two or more primary tumors cannot be enrolled, except for cured carcinoma in situ and basal cell carcinoma. Subjects with concomitant tumors that have been stable for more than 5 years before enrollment in the study can be enrolled;
•Subjects who have active auto-immune diseases requiring systemic treatment with immunomodulatory drugs within 12 months prior to treatment initiation, but relevant alternative therapies are allowed;
•Subjects who have received systemic treatment with corticosteroids (more than 10 mg/day prednisone equivalent) or other immunosuppressants for more than 7 days within 2 weeks prior to treatment initiation (inhaled or topical steroids or adrenal replacement therapy in excess of 10 mg prednisone equivalents is permitted in the absence of active auto-immune disease);