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Therapex Launches Attack on Tagrisso-Resistant Lung Cancer with Targeted Anticancer Agent 'TRX-221'
NOTICE
2024-03-26
Approval of an Investigational New Drug application (IND) for the Phase 1/2 study of EGFR-TKI Resistant Non-Small Cell Lung Cancer Patients on January 21st
TRX-221 targets the 'EGFR C797S' mutation that frequently occurs with
resistance to Tagrisso
Therapex, a specialized company in the
development of targeted anticancer agents for the treatment of intractable
tumor, is embarking on clinical trials to develop effective anticancer drugs
for patients resistant to third-generation EGFR-TKIs (epidermal growth factor
receptor (EGFR)-tyrosine kinase inhibitors) such as Tagrisso (containing
Osimertinib).
Therapex, a subsidiary of Gradient, originated from Interpark Bio Convergence’s
in-house Research Institute in 2017 and was formally established as a corporation
in July 2020. Under the name "Interpark Bio Convergence," the company
underwent a split-off and spin-off with Gradient Bio Convergence in 2022, subsequently
changing its name to its current one.
On the 21st, Therapex received approval for its IND application from
the Ministry of Food and Drug Safety of the Republic of Korea, allowing it to
begin its Phase 1/2 study of the targeted anticancer agent TRX-221. This Phase
1/2 trial is an open-label multicenter study of TRX-221 in patients with
EGFR-mutated non-small cell lung cancer who have previously received therapy
with EGFR-TKIs to explore safety, tolerability, pharmacokinetics, and antitumor
activity.
The clinical trial is set to commence patient dosing next month, with a target
of 77 patients in South Korea and 115 globally. The trial will be conducted in
clinical trial sites including △Chungbuk National University Hospital, △Samsung
Medical Center, △Seoul Asan Medical Center, and △Yonsei University Severance
Hospital.
Looking at the clinical trial protocol, the primary efficacy endpoint for the
Phase 2 clinical trial is Objective Response Rate (ORR), and the secondary
efficacy endpoint includes ΔDuration of Response (DOR), ΔDisease Control Rate
(DCR), ΔProgression-Free Survival (PFS), ΔOverall Survival (OS), Δincidence and
severity of Adverse Events (AE) classified according to NCI-CTCAE v5.0, and
Δthe number and proportion of patients experiencing Treatment-Emergent Adverse
Events (TEAE) and Serious Adverse Events (SAE), as well as Δsafety and tolerability
based on clinical laboratory tests, vital signs, physical examinations, and
12-lead ECG. This design mirrors the IND application that was approved by the
U.S. Food and Drug Administration (FDA) in August last year.
According to Therapex, TRX-221 is a targeted anticancer agent that selectively
inhibits EGFR mutations, which account for 20% of non-small-cell lung cancers. The
EGFR-TKI mechanism involves inducing cell death by selectively and strongly
binding only to the tyrosine kinase domain of EGFR mutations, thereby
inhibiting the expression of downstream signaling molecules.
This new drug candidate is often referred to as a fourth-generation EGFR-TKI by
targeting progressive non-small-cell lung cancer with the most frequently
occurring ‘EGFR C797S mutation’, which arises from resistance to Tagrisso, the
standard of care (SOC) for EGFR-mutant non-small-cell lung cancer.
A representative from Therapex stated in an interview with Hit News that
"The Phase 1 part of the ongoing Phase 1/2 trial will progress through
dose escalation to dose exploration. The goal is to evaluate safety and
tolerability through stepwise dose escalation and determine the maximum
tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of the drug." He
added, "To expedite the clinical trial, dose escalation will be conducted
in South Korea only, and from the dose exploration stage onwards, it will be
conducted globally to increase patient enrollment."
He continued, "TRX-221 aims to target progressive EGFR(C797S)-mutant
non-small-cell lung cancer, which frequently occurs in patients receiving
Tagrisso." He further explained, "TRX-221 has demonstrated excellent
anticancer efficacy in various PDX mouse models, which are highly
physiologically relevant to tumor biology in patients with actual C797S
mutations, in a preclinical study."
The company plans to expand indications to include EGFR mutations (exon 19
deletion, exon 21 [L858R] substitution) and T790M, a resistance mutation to the
first-generation targeted drugs including Iressa (Gefitinib) and Tarceva
(Erlotinib), if the safety of TRX-221 is confirmed in this Phase 1 study.
Additionally, the company plans to conduct research targeting MET gene
amplification, known for Tagrisso resistance, in non-small-cell lung cancer
patients.
A company representative stated, "Therapex is considering combining
therapy with drug targeting MET gene amplification to meet various medical
unmet needs and is currently preparing for further study at the preclinical
trial level.”
Meanwhile, the company plans to initiate the first patient dosing (FPI) next
month and pursue out-licensing alongside the Phase 1a trial. A company representative
remarked, "Looking at the past case of Leclaza (active ingredient:
Lazertinib), discussions with Janssen were initiated, and a contract was subsequently
signed, once Phase 1 clinical safety results were obtained.”
Furthermore, he added, "Based on the preclinical study results of TRX-221,
we anticipate that we can smoothly proceed with dose escalation trials until
reaching the clinically effective dose within the company." He continued,
"To maximize the value of TRX-221, we also plan to conduct scientific
interpretation (scientific rationale) of clinical combination therapy and
explore partnerships."
Source: Hit News, Reporter Hwang Jaesun
(http://www.hitnews.co.kr)