First Patient Receives KSQ-004EX for Advanced Cancer

Cancer cells, 3D illustration: © Dr_Microbe - stock.adobe.com

A phase 1/2 trial evaluating KSQ-004EX, a novel CRISPR-engineered tumor infiltrating lymphocyte (eTIL) therapy, has dosed its first patient with an advanced solid tumor.¹

This first patient was enrolled by Rodabe Amaria, MD, professor of melanoma medical oncology and principal investigator of the study at The University of Texas MD Anderson Cancer Center.

“The promise of TIL therapy remains high, but current approaches fall short of addressing the needs of most patients with solid tumors. Preclinically, the combined inactivation of SOCS1 and Regnase-1 in KSQ-004EX strongly increased anti-tumor functionality. We believe these enhancements give KSQ-004EX the potential to significantly advance TIL therapy for the treatment of solid tumors,” said Qasim Rizvi, chief executive officer of KSQ and chief executive officer-partner at Flagship Pioneering, in a press release.

KSQ-004EX is an investigational eTIL therapy. Utilizing CRISPR/Cas9 gene editing, this approach involves the inactivation of SOCS1 and Regnase-1. This dual gene inactivation is designed to enhance the functionality of the infused TILs.¹

In the phase 1/2, open-label, dose-escalation study, investigators are evaluating KSQ-004EX for the treatment of patients with advanced solid tumors. These include melanoma, non–small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer, pancreatic cancer, and cervical cancer.

Eligible patients must have progressed on prior systemic therapy for unresectable/metastatic melanoma after anti–PD-1/PD-L1, with or without anti–CTLA-4/LAG-3, NSCLC after platinum-based chemotherapy and checkpoint inhibitor, plus targeted therapy if applicable, or HNSCC that has been treated with 1 to 3 prior lines, including platinum and anti-PD-1/PD-L1.² Patients also must have a resectable lesion for manufacturing and at least one measurable lesion post-resection RECIST v1.1. Additional criteria include being aged 18 to 70 years, having an ECOG performance status of 0 or 1, and having adequate organ function.

In the phase 1 safety lead-in (cohort 1), roughly 6 patients with melanoma, NSCLC, or HNSCC will receive a KSQ-001EX dose. Cohort 2 will involve approximately 6 patients receiving IL-2 at a dose of 600,000 IU/kg every 8 to 12 hours, up to 6 doses as tolerated. The phase 2 expansion (arm 3) anticipates enrolling around 20 patients in separate cohorts for each of the 3 indications.

The primary end point of the phase 1 portion of the trial is to evaluate the safety and tolerability of KSQ-004EX. For phase 2, the primary end point is to evaluate antitumor activity in indication-specific cohorts.

References:

1. KSQ Therapeutics announces first patient dosed in phase 1/2 study for KSQ-004EX, a CRISPR/Cas9-engineered tumor infiltrating lymphocyte (eTIL®) therapy. News release. KSQ Therapeutics, Inc. April 9, 2025. Accessed April 9, 2025. https://tinyurl.com/yc7xxy3r

2. A phase 1/​2 study of KSQ-001EX, autologous tumor infiltrating lymphocytes engineered to inactivate the SOCS1 gene, in patients with select advanced solid tumors. ClinicalTrials.gov. April 9, 2025. Accessed April 9, 2025. https://clinicaltrials.gov/study/NCT06237881?term=KSQ-001%20EX&rank=1