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

Therapex

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: TRX-221

Study type: Interventional

Funder types: Industry

Identifiers

NCT06186076

TRX-221-001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 115 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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115 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: TRX-221

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

Experimental group

Description:

All eligible patients will receive the study treatment at selected oral dose(s) once daily. Dose-levels will be selected from the Part A.

Treatment:

Drug: TRX-221

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

Experimental group

Description:

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

Treatment:

Drug: TRX-221