FDA Grants Clearance for Phase 1/2 Trial of eTIL KSQ-001EX in Solid Tumors

November 30, 2023

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The FDA has granted clearance for an investigational new drug application for a phase 1/2 safety lead-in trial investigating the engineered tumor-infiltrating lymphocyte KSQ-001EX in patients with melanoma, head and neck squamous cell carcinoma, and non–small cell lung cancer.

FDA

The FDA has granted clearance for an investigational new drug application for a phase 1/2 safety lead-in trial investigating the engineered tumor-infiltrating lymphocyte (eTIL) KSQ-001EX in patients with melanoma, head and neck squamous cell carcinoma, and non–small cell lung cancer.¹

The primary objective of the phase 1 portion of the trial will be to examine the safety and tolerability of KSQ-001EX. In the safety lead-in portion of the trial, a cohort of patients will initially receive KSQ-001EX without interleukin-2. In the phase 2 portion of the trial, the primary objective will be to investigate antitumor activity in indication-specific cohorts of patients.

KSQ-001EX comprises TILs in which CRISPR/Cas9 gene editing inactivates the SOCS1 gene. SOCS1 is a key gene for regulating the antitumor persistence and potency of TILs.

“Our team has made great progress advancing our KSQ-001EX and KSQ-004EX eTIL^® programs,” Qasim Rizvi, chief executive officer of KSQ Therapeutics, stated in a news release. “Through our platform insights, we’ve identified how to enhance the effectiveness of T cells in the treatment of solid tumors. We believe our eTIL® cell therapies have tremendous potential to benefit patients with cancer who have limited treatment options. We look forward to working closely with the clinical experts at [The University of Texas] MD Anderson [Cancer Center in Houston], where the study will be initiated. Our partnership with CTMC has yielded a robust manufacturing process for our eTIL® cell therapy that is derived from patient tumor samples, including core biopsies.”

“New treatment options are urgently needed in melanoma and other solid tumors, and the potential to improve outcomes and patient experience is very exciting,” Rodabe Amaria, MD, a professor of melanoma medical oncology at MD Anderson Cancer Center and the principal investigator of the phase 1/2 trial, added in the news release.

Preclinical studies with KSQ-001EX have demonstrated enhanced antitumor function in solid tumors that are refractory to PD-1 inhibition, as well as memory formation and enhanced persistence.

Additionally, a preclinical study examined the eTIL KSQ-001, which was manufactured from human melanoma TILs and created by CRISPR/Cas9-mediated CT-1 editing.² This study initially found that CT-1–edited murine KSQ-001 TILs are 10 times more potent than control edited T cells, and that 21 days post–adoptive transfer, murine KSQ-001 TILs are found at frequency levels in the peripheral blood that are 5 times higher than the frequency levels of control-edited T cells.

This study also found that human-derived KSQ-001 secreted higher amounts of IFNγ and TNFα following anti-CD3 stimulation compared with control genes CT-1 and OR1A1. Moreover, TILs from a donor with HLA-A2–positive disease contained specificity for the Mart-1 tumor antigen. Following the rapid expansion phase of the trial, KSQ-001 manufactured from this donor retained Mart-1 specificity at levels similar to control-edited TILs. Furthermore, when mRNA from 5 KSQ-001 and control samples were run on the Nanostring CAR-T Characterization Panel, KSQ-001 exhibited increased expression of T-cell activation markers, cytokines, cytokine signaling, cytolytic proteins, and T-cell signaling pathway components compared with control TILs.