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

NCT06186076 | Terminated Phase 1 FDA Drug

• 1 other identifier: TRX-221-001
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Carcinoma, Non-Small-Cell Lung; EGFR Mutant Advanced Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• [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 Outcomes (4)

• To characterize the PK profile of the study treatment

  Throughout the study period, an average of 1 year

• To evaluate the preliminary anti-tumor activity of the study treatment (Phase 1)

  Approx. 12 months

• To evaluate additional anti-tumor activity of the study treatment other than the primary endpoint (Phase 2)

  Approx. 12 months

• To assess the safety and tolerability of the study treatment (Phase 2)

  Approx. 12 months

Study Arms (3)

Phase 1 Part A: Dose escalation in patients with EGFR sensitizing mutation

EXPERIMENTAL

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

Phase 1 Part B: 2 dose levels of TRX-221 in patients with EGFR sensitizing mutation

EXPERIMENTAL

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

Phase 2: Recommended Phase 2 dose(s) of TRX-221 in patients with EGFR C797X mutation

EXPERIMENTAL

All eligible patients will receive the study treatment at selected oral dose(s) once daily.

Drug: TRX-221

Interventions

TRX-221 DRUG

TRX-221 oral dose as defined

Phase 1 Part A: Dose escalation in patients with EGFR sensitizing mutation; Phase 1 Part B: 2 dose levels of TRX-221 in patients with EGFR sensitizing mutation; Phase 2: Recommended Phase 2 dose(s) of TRX-221 in patients with EGFR C797X mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• NSCLC with mixed cell histology or a tumor with histologic transformation of small cell elements
• Patients having tumor with any additional known driver of alterations
• 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
• 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
• Patients having clinically active ongoing ILD of any etiology
• Clinically significant cardiac conditions, infections, refractory GI diseases as specified in the protocol
• 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
• Recent anticancer therapy: EGFR-TKI, Immunotherapy or any other systemic anticancer therapy or radiotherapy (specific duration prior to starting study medication per protocol)

Sponsors & Collaborators

• Therapex Co., Ltd: lead

Study Sites (6)

Seoul National University Bundang Hospital

Seongnam, Kyeongki, 13620, South Korea

Location

The Catholic University of Korea St. Vincent Hospital

Suwon, Kyeongki, 16247, South Korea

Location

Chungbuk National University Hospital

Chungju, North Chungcheong, 28644, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Therapex Co., Ltd Clinical Development

  Therapex Co., Ltd: Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 29, 2023
• Study Start: June 14, 2024
• Primary Completion: December 3, 2025
• Study Completion: December 3, 2025
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (6)