Clinical trial NCT06186076: A Study to Investigate Safety, Tolerability, PK and Anti-tumor Activity of TRX-221 in EGFRm NSCLC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
EGFR Mutant Advanced Non-Small Cell Lung Cancer
Lead sponsor: Therapex Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-12-29
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: [Phase1 PartA: Dose Escalation] To assess the safety/tolerability and determine the MTD/RP2D range of TRX-221
timeFrame: Approx. 12 months
measure: [Phase1 PartB: Dose Exploration] To determine the RP2D of TRX-221
timeFrame: Approx. 6-12 months
measure: [Phase2] To assess the anti-tumor activity of TRX-221 in patients with the selected EGFR-resistant mutation type
timeFrame: Approx. 6-12 months
Secondary outcomes:
measure: To characterize the PK profile of the study treatment
timeFrame: Throughout the study period, an average of 1 year
measure: To evaluate the preliminary anti-tumor activity of the study treatment (Phase 1)
timeFrame: Approx. 12 months
measure: To evaluate additional anti-tumor activity of the study treatment other than the primary endpoint (Phase 2)
timeFrame: Approx. 12 months
measure: To assess the safety and tolerability of the study treatment (Phase 2)
timeFrame: Approx. 12 months
Other outcomes:
Locations:
city: Chungju
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungbuk
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyeongki
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent Hospital
state: Kyeongki
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Therapex Co., Ltd: Clinical Development
name: Therapex Co., Ltd Clinical Development
role: STUDY_DIRECTOR
References: