Clinical Trials/NCT05441956

NCT05441956

Active, not recruiting

Phase 1

A Dose Escalation and Expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TGRX-326 Monotherapy for the Treatment of Advanced ALK-positive or ROS1-positive Non-Small Cell Lung Cancer

Shenzhen TargetRx, Inc.1 site in 1 country198 target enrollmentApril 23, 2021

ConditionsNon-small Cell Lung Cancer

InterventionsTGRX-326

DrugsTGRX-326

Overview

Phase: Phase 1
Intervention: TGRX-326
Conditions: Non-small Cell Lung Cancer
Sponsor: Shenzhen TargetRx, Inc.
Enrollment: 198
Locations: 1
Primary Endpoint: Maximal tolerated dose (MTD)
Status: Active, not recruiting
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This trial is a multi-center, single-arm, open-label, Phase I clinical trial in 3 phases: dose escalation phase, dose expansion phase and indication expansion phase, which will explore the safety, tolerability, PK and preliminary efficacy of TGRX-326 in patients with ALK-positive or ROS1-positive advanced NSCLC.

Detailed Description

This is the first-in-human trial with TGRX-326 which aims to evaluate the safety profile and preliminary efficacy profile in patients with ALK-positive or ROS1-positive advanced NSCLC. The primary purpose of this study is to evaluate the safety profile of TGRX-326, including determination of the maximal tolerated dose (MTD) and recommended phase II dose (RP2D), and other safety measures of the investigational drug, such as adverse events and abnormal clinical outcomes. Preliminary efficacy profiles of TGRX-326 is also evaluated according to RECIST Version 1.1. The safety, tolerability and efficacy profiles, along with pharmacokinetic analysis, will be assessed together to determine the optimal dose for expansion.

Registry

clinicaltrials.gov

Start Date

April 23, 2021

End Date

October 31, 2025

Last Updated

11 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shenzhen TargetRx, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willing to follow the treatment protocol and visit schedule, and participate in the study with the ICF signed;
•≥ 18 years of age on the day of ICF signing, regardless of gender.
•Diagnosis of ALK-positive or ROS1-positive advanced NSCLC by histopathology or cytology in a Grade-A tertiary hospital or central laboratory.
•Provision of the following information: archived tissue samples and/or fresh tumor tissue samples obtained during the screening period for biomarker detection; previous biomarker detection results from a Grade-A tertiary hospital (exempt from the above-mentioned biomarker detection); previous NGS results; the consent of medical monitors for the participation of subjects who fail to provide tumor tissue samples (e.g., samples are exhausted due to previous diagnostic tests but high clinical risk may be brought about by re-puncture, etc.).
•Metastases to central nervous system (CNS) with the following conditions met: a. asymptomatic: no current need for corticosteroid therapy, or only stable dose or a dose reduced to ≤ 10 mg of prednisone (QD) or equivalent required; or b. past diagnosis, treatment completed, complete recovery from acute effects of radiation therapy or surgery prior to the first dose, discontinuation of corticosteroid therapy for these metastases for at least 4 weeks, and neurologically stable;
•Drug discontinuation for ≥ 5 half-lives prior to the first dose for subjects previously treated with a targeted therapy (e.g., ALK or ROS1 inhibitors);
•At least one measurable (longest diameter for non-lymph nodes: ≥ 10 mm; shortest diameter for lymph nodes: ≥ 15 mm) target lesion (a previously irradiated lesion cannot be regarded as a target lesion unless it is significantly progressive) according to criteria in RECIST version 1.1;
•Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0-1 point in dose escalation and dose expansion phases; 0-2 points in indication expansion phase;
•Recovery from any AEs associated with prior surgery and cancer therapy (to ≤ Grade 1), with the following exceptions: a. alopecia; b. pigmentation; c. long-term toxicity due to radiotherapy that, in the judgment of the investigator, is not recoverable; d. Grade 2 and below neurotoxicity due to platinum; e. hemoglobin within the range of 90-100 g/L (inclusive);
•Adequate bone marrow, liver, kidney, coagulation and pancreatic functions;

Exclusion Criteria

•Previous use of any third-generation ALK inhibitors or second-generation ROS1 inhibitors other than TGRX-
•Known hypersensitivity to any of the active ingredients or excipients of TGRX-326; an identified history of allergy to protein-based drugs; a history of atopic allergy (asthma, rheumatism, eczematous dermatitis); previous history of other severe allergic reactions that makes himself/herself unsuitable for TGRX-326 treatment in the judgment of the investigator;
•Having another type of cancer except for lung cancer, excluding malignant tumors including cervical cancer in situ and non-melanoma skin cancer that have been curatively treated and have not recurred within 5 years;
•Having previously received antibodies or pharmacotherapy against T cell costimulation or immune checkpoint pathways, including but not limited to anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death protein ligand 1 (anti-PD-1), anti-programmed cell death protein ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137) antibody or anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody;
•Major surgery within 4 weeks prior to the first dose. Minor surgery such as infusion port placement is not listed in the exclusion criteria, but sufficient time is required to achieve adequate wound healing;
•Spinal cord compression, unless the subject achieves significant pain control with treatment and full recovery of neurological function within 4 weeks prior to the first dose.
•Abnormal gastrointestinal function, including the inability to take oral drugs, the need for intravenous nutrition, previous surgical operations (including total gastrectomy or gastric band surgery) that affect absorption, active inflammatory gastrointestinal diseases, chronic diarrhea, symptomatic Diverticular disease, treatment of active peptic ulcer disease or malabsorption syndrome within the past 6 months;
•History of active pneumonia or interstitial pneumonia, or radiation or drug-induced lung disorder on CT at screening. Radiation pneumonia patients without clinical symptoms 3 months after radiotherapy are allowed to be enrolled;
•Cardiac insufficiency, including but not limited to left ventricular ejection fraction (LVEF) \< 50%, history of congestive cardiac failure, ventricular arrhythmia requiring treatment, hypokalemia, hereditary long QT syndrome, or history of myocardial infarction or unstable angina pectoris within 6 months before screening; ≥ Class 2 heart failure in New York Heart Association Classification;
•Abnormal and clinically significant QTc on ECG (\> 450 msec \[male\] or QTc \> 470 msec \[female\] at rest); concomitant use of any drug known to prolong QT interval and cause torsades de pointes;

Arms & Interventions

TGRX-326

Subjects to be treated with the investigational drug TGRX-326

Intervention: TGRX-326

Outcomes

Primary Outcomes

Maximal tolerated dose (MTD)

Time Frame: At end of Cycle 1 (each cycle is 21 days) when the probability of DLT of a dose level is higher than 33%

To determine the MTD of TGRX-326 in NSCLC patients

Safety profile (AEs/SAEs)

Time Frame: Through completion of the study, an average of 1.5 years

To record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)

Recommended phase II dose (RP2D)

Time Frame: At completion of the dose expansion study, an average of 1 year

To determine the RP2D of TGRX-326 in NSCLC patients for Phase II

Safety profile (DLT)

Time Frame: Collect during Cycle 1 (each cycle is 21 days)

To record and analyse subjects with dose-limiting toxicities (DLTs)

Secondary Outcomes

Plasma AUCinf(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma Cmax(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma Tmax(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma AUCss(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma Tmax,ss(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
T1/2(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma Cmin(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma T1/2,ss(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Plasma Cmax,ss(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
CL(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
Vd(Day1/3 of single-dose period; Day1/8/15 of Cycle 1; Day1 of Cycle 2-5, Day 1 of every other cycle starting from Cycle 7; Day 1 of every 4 cycles starting from Cycle 17 (each cycle is 21 days))
IC-ORR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))
DCR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))
DOR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))
IC-DOR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))
ORR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))
IC-DCR(At screening, Day 1 of every other cycle starting from Cycle 3, and Day 1 of every 4 cycles starting Cycle 17 (each cycle is 21 days))