TR115 in Patients With Relapsed / Refractory Non-Hodgkin's Lymphoma or Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
A phase 1 dose escalation and expanded cohort study of TR115 in the treatment of adult patients with relapsed/refractory non-hodgkin's lymphoma or advanced solid tumors.

Detailed Description
-----------------
This is a open-label, dose escalation and expansion, accelerated titration combined 3+3 design, phase 1 study, to evaluate the safety and tolerability, and to determine the Recommeded Phase II Dose (RP2D) of TR115 when administered bid in patients with non-hodgkin's lymphoma or advanced solid tumors. During the dose escalation phase, Up to 6 cohorts of 1-6 0r 3-6 patients each will be treated in the study. Patients will receive study treatment until criteria for study termination are met. A safety Follow-up Visit will conducted 30 days (±7 days) after the last dose of treatment. Patients who discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, lost to follow-up, death, or until the sponsor stops the study, whichever comes first. After finishing the dose escalation phase, a dose extension phase will be initiated with additional patients included in order to further evaluate the tolerability, pharmacokinetics, and efficacy at the recommended dose that have been evaluated in the dose escalation phase. Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Tumor response will be assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) scan using Lugano 2014/RECIST 1.1 criteria, assessed by the investigator.

Official Title
-----------------
A Phase I Clinical Study to Characterize Safety, Tolerability, and Pharmacokinetics of TR115 in Patients With Relapsed / Refractory Non-Hodgkin's Lymphoma or Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumor, Non-Hodgkin's Lymphoma, Relapsed, Non-Hodgkin's Lymphoma Refractory

Intervention / Treatment
-----------------
* Drug: TR115


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol. males and/or females at least 18 years old when signing the informed consent form. tumor type criteria: relapsed/refractory histologically or cytologically documented non-hodgkin's lymphoma must have received at least 1 prior systemic therapies, including but not limited as below: Follicular Lymphoma (FL), Diffuse Large B-cell Lymphoma (DLBCL), Peripheral T-cell lymphoma-Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL), Anaplastic Large Cell Lymphoma (ALCL). histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator. eastern cooperative oncology group performance status (ECOG) ≤2 at screening. life expectancy of at least 3 months. acceptable organ function: absolute neutrophil count (ANC)≥1.0×109/L (note: growth factor supports within 14 days of the first dose); platelet count (PLT)≥90×109/L （note: PLT≥70 × 109/L for patients with Non-Hodgkin Lymphoma (NHL) and ≥50 × 109/L allowed in patients with bone marrow infiltration. no blood product transfusion is allowed within 14 days of the first dose); hemoglobin (Hb) ≥90g/L (note: Hb ≥80g/L for patients with NHL and ≥70g/L in patients with bone marrow infiltration. no blood product transfusion is allowed within 14 days of the first dose); International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5×Upper limit of normal value (ULN), Activated Partial Thromboplastin Time (APTT)≤1.5×ULN ；Total bilirubin (TBIL)≤1.5×ULN, Aspartate Amino Tranferase (AST) and Alanine Transaminase (ALT)≤2.5×ULN (note: ≤ 5 × ULN if there is liver involvement); Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50 ml/min (calculated by Cockcroft-Gault formula). fertile male and female must agree to use medically approved contraceptives during the study and within 6 months after the last dose of the study. Key Exclusion Criteria: known or suspected allergies to any of the investigational drug compositon. medical history and surgical history excluded according to the protocol. any previous medical treatment history exclude from the protocol. abnormal laboratory results exclude from the protocol. pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding). subjects may not be able to complete the study due to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation and Expansion<br>Participants with relapsed/Refractory Non-Hodgkin's Lymphoma or Advanced solid tumor will receive TR115 at escalating and expansion dose levels. | Drug: TR115<br>* TR115 is supplied as tablet with dosage strength of 100mg. TR115 tablet will be administered orally on a continuous twice daily (BID) schedule and a treatment cycle is defined as 28 days for the purposes of scheduling procedures and evaluations. TR115 tablets will be given until there appears evidence of progressive disease , intolerable toxicity, or the subject discontinues from the study treatment for other reasons. Proposed daily dose (BID): 100mg, 200mg, 400mg, 800mg, 1200mg, 1600mg. It is possible for additional and/or intermediate dose levels to be added during the course of the study. Cohorts may be added at any dose level below the Maximum Tolerated Dose (MTD) in order to better understand safety, Pharmacokinetic (PK) or Pharmacodynamic (PD).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and serious adverse events | frequency, duration and severity of adverse events and serious adverse events evaluated by NCI CTCAE 5.0 | from the first dose to within 30 days after the last dose | 
| dose limited toxicities | incidence of dose limited toxicities | within 31 days after the first dose | 
| maximum tolerated dose | evaluated by safety review committee | Throughout the study for approximately 2 years | 
| recommedded phase 2 dose | evaluated by safety review committee | Throughout the study for approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| AUCinf | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| Cmax | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| Tmax | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| CL/F | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| Vz/F | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose | 
| Terminal half-life (T1/2) | characterize the pharmacokinetic profile of TR115 | within 31 days after the first dose |