A Study to Investigate Safety, Tolerability, PK and Anti-tumor Activity of TRX-221 in EGFRm NSCLC Patients

An Open Label, Multicenter, Phase 1/2 Study to Explore the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of TRX-221 in the Treatment of Patients With EGFR Mutant NSCLC Who Progressed Following Prior Therapy With EGFR TKI

This is a Phase 1/2, open-label study designed to investigate the safety, tolerability, PK, and anti-tumor activity of the study treatment in the treatment of patients with EGFR mutant NSCLC, who progressed following prior standard treatments which include the approved EGFR-TKIs with activity against T790M (e.g., osimertinib).

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung; EGFR Mutant Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: TRX-221

Detailed Description

All eligible patients will receive the study treatment at selected oral dose(s) once daily. Patients will be treated continuously until disease progression or any other pre-defined discontinuation criteria are met.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Kyeongki
    • Seongnam, Kyeongki, South Korea, 13620
      • Seoul National University Bundang Hospital
    • Suwon, Kyeongki, South Korea, 16247
      • The Catholic University of Korea St. Vincent Hospital
  • North Chungcheong
    • Chungju, North Chungcheong, South Korea, 28644
      • Chungbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with ECOG performance status score of 0 or 1
2. Histologically or cytologically confirmed diagnosis of relapsed or refractory, locally unresectable advanced or metastatic NSCLC harboring an activating EGFR mutation
3. Failed standard of care treatments progressed after anti tumor treatments including at least 1 approved EGFR TKI [Phase2: TKIs should include the approved EGFR TKIs with activity against T790M (e.g., osimertinib)]
4. Slots may be reserved for patients with certain resistant mutations (i.e., EGFR C797X mutation with or without T790M mutation as required by the sponsor) [Phase 1]
5. EGFR C797X mutation with or without T790M mutation [Phase 2]
6. Not received more than 1 prior line of platinum based chemotherapy in the metastatic setting [Phase 2]
7. Having at least 1 measurable tumor lesion per RECIST v1.1 criteria [Phase 2]
8. Having adequate bone marrow, hepatic, and renal function as specified in the protocol

Exclusion Criteria:

1. NSCLC with mixed cell histology or a tumor with histologic transformation of small cell elements
2. Patients having tumor with any additional known driver of alterations
3. Patients with presence of another active primary malignant tumor that has been diagnosed or required therapy within 2 years prior to the initiation of the study treatment
4. Patients who have unstable and symptomatic primary CNS tumors/metastasis, leptomeningeal metastases or spinal cord compression which are not suitable for enrollment, as judged by the Investigator
5. Patients having clinically active ongoing ILD of any etiology
6. Clinically significant cardiac conditions, infections, refractory GI diseases as specified in the protocol
7. Patients having any unresolved toxicities from prior anti tumor therapy and surgery greater than CTCAE Grade 1 at the time of starting the study treatment
8. Recent anticancer therapy: EGFR-TKI, Immunotherapy or any other systemic anticancer therapy or radiotherapy (specific duration prior to starting study medication per protocol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Part A: Dose escalation in patients with EGFR sensitizing mutation; All eligible patients will receive the study treatment at selected oral dose(s) once daily, as per the assigned dose level from the pre-defined escalation scheme and SRC(Safety Review Committee) decision.	Drug: TRX-221; TRX-221 oral dose as defined
Experimental: Phase 1 Part B: 2 dose levels of TRX-221 in patients with EGFR sensitizing mutation; All eligible patients will receive the study treatment at selected oral dose(s) once daily. Dose-levels will be selected from the Part A.	Drug: TRX-221; TRX-221 oral dose as defined
Experimental: Phase 2: Recommended Phase 2 dose(s) of TRX-221 in patients with EGFR C797X mutation; All eligible patients will receive the study treatment at selected oral dose(s) once daily.	Drug: TRX-221; TRX-221 oral dose as defined

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Phase1 PartA: Dose Escalation] To assess the safety/tolerability and determine the MTD/RP2D range of TRX-221	Incidence and severity of AEs graded according to the NCI-CTCAE v5.0 Number and percentage of patients with TEAEs, SAEs, and DLTs Safety and tolerability as noted by laboratory data, vital signs, physical examinations, and 12-lead ECGs	Approx. 12 months
[Phase1 PartB: Dose Exploration] To determine the RP2D of TRX-221	Incidence and severity of AEs, TEAEs, SAEs Safety and tolerability as noted by laboratory data, vital signs, physical examinations, and 12-lead ECGs	Approx. 6-12 months
[Phase2] To assess the anti-tumor activity of TRX-221 in patients with the selected EGFR-resistant mutation type	Tumor response rate (ORR)	Approx. 6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the PK profile of the study treatment	Peak Plasma Concentration (Cmax)	Throughout the study period, an average of 1 year
To evaluate the preliminary anti-tumor activity of the study treatment (Phase 1)	ORR	Approx. 12 months
To evaluate additional anti-tumor activity of the study treatment other than the primary endpoint (Phase 2)	PFS	Approx. 12 months
To assess the safety and tolerability of the study treatment (Phase 2)	Incidence and severity of AEs, TEAEs, SAEs Safety and tolerability as noted by laboratory data, vital signs, physical examinations, and 12-lead ECGs	Approx. 12 months

Collaborators and Investigators

• Sponsor: Therapex Co., Ltd
• Investigators: Study Director: Therapex Co., Ltd Clinical Development, Therapex Co., Ltd: Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2024
• Primary Completion (Actual): December 3, 2025
• Study Completion (Actual): December 3, 2025

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: TRX-221-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No