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FDA Approves Phase 1/2 Clinical Trial for REC-4539 in Small Cell Lung Cancer

The FDA has cleared an investigational new drug application for REC-4539, a novel LSD1 inhibitor, marking the start of a phase 1/2 clinical trial targeting small cell lung cancer (SCLC) and other solid tumors. REC-4539 is distinguished by its CNS-penetrant and reversible properties, aiming to minimize platelet-related toxicities and improve safety profiles. The trial, named ENLYGHT, will explore REC-4539's efficacy both as a monotherapy and in combination with durvalumab, with patient dosing expected to begin in the first half of 2025.

FDA Clears IND Application for REC-4539

The U.S. Food and Drug Administration (FDA) has recently cleared an investigational new drug (IND) application for REC-4539, initiating a phase 1/2 clinical trial. This novel lysine-specific demethylase 1 (LSD1) inhibitor is set to be evaluated for its potential in treating small cell lung cancer (SCLC) and several other solid tumor indications.

REC-4539: A Novel Approach to LSD1 Inhibition

REC-4539 stands out as the first LSD1 inhibitor designed to be both CNS-penetrant and reversible. This characteristic is crucial for targeting both peripheral and central nervous system (CNS) diseases effectively. LSD1 overexpression has been linked to the proliferation and survival of various tumors, including SCLC. REC-4539's selective inhibition of LSD1 aims to offer a therapeutic advantage by potentially minimizing platelet-related toxicities, such as thrombocytopenia, which are commonly associated with this class of drugs.

Preclinical Success and Clinical Prospects

In preclinical studies, REC-4539 demonstrated promising results, including dose-dependent tumor inhibition in SCLC xenograft models and effective brain penetration. These studies also suggested an improved safety profile compared to other LSD1 inhibitors currently in clinical development, with limited effects on platelet levels indicating a reduced risk for thrombocytopenia. Furthermore, REC-4539 exhibited a favorable absorption, distribution, metabolism, and excretion profile, with a shorter half-life in humans compared to other LSD1 inhibitors.

The ENLYGHT Trial: A Dual Approach

The phase 1/2 ENLYGHT trial is designed to evaluate REC-4539 both as a monotherapy and in combination with durvalumab (Imfinzi), an anti-PD-L1 antibody, in patients with extensive-stage SCLC. The trial aims to assess the efficacy of REC-4539 in improving radiographic progression-free survival and overall survival, while also focusing on minimizing common adverse events associated with LSD1 inhibition, particularly thrombocytopenia.

Looking Ahead

Patient dosing in the ENLYGHT trial is expected to commence in the first half of 2025, with results anticipated in the following years. Beyond SCLC, REC-4539 is also being developed for other indications, including acute myeloid leukemia, highlighting its potential as a versatile therapeutic agent in the fight against cancer.
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Reference News

[1]
FDA Clears Investigational New Drug Application for REC-4539 in SCLC
targetedonc.com · Jan 8, 2025

The FDA approved REC-4539, a novel LSD1 inhibitor, for a phase 1/2 trial targeting small cell lung cancer and other soli...

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