A phase 1/2 study of KSQ-004EX: Autologous tumor infiltrating lymphocytes, engineered to inactivate genes encoding SOCS1 and Regnase-1, in patients with select advanced solid tumors.
Background: The effectiveness and durability of TIL therapy may be limited by the immunosuppressive tumor microenvironment and baseline functionality of transferred T cells. Through KSQ Therapeutics’ CRISPR2 platform, a novel method for screening optimal combinatorial targets for enhancing T cell anti-tumor efficacy in vivo, SOCS1 and Regnase-1 were identified as the most potent gene editing combination. KSQ-004EX, an engineered TIL product with CRISPR/Cas9 mediated dual-inactivation of SOCS1 and Regnase-1, is anticipated to in enhance T cell tumor infiltration, persistence, and efficacy. This first-in-human clinical study (NCT06598371) evaluates KSQ-004EX in patients with melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), colorectal carcinoma (CRC), pancreatic cancer, and cervical cancer. Methods: The phase 1/2, single-arm, open-label study will assess the safety, tolerability, and efficacy of KSQ-004EX in patients with select advanced solid tumors. Patients with melanoma, NSCLC, HNSCC, CRC, pancreatic, and cervical cancer who have progressed following treatment with 1 to 3 lines of prior standard therapy including standard directed therapy (as applicable), are eligible. KSQ-004EX is manufactured from the patient’s tumor, which is collected through surgical resection or core needle biopsy. All patients must have at least 1 measurable lesion following resection. Patients receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine prior to KSQ-004EX infusion. Patients in the initial dose escalation cohorts do not receive dosing with IL-2; IL-2 dosing may be included in subsequent cohorts. Approximately 6 patients will be enrolled in Phase 1 dose escalation, in escalating dose levels. The primary objective of Phase 1 is to evaluate the safety and tolerability of KSQ-004EX. In Phase 2, patients will be enrolled in indication-specific cohorts. The primary objective of Phase 2 is to assess the anti-tumor activity of KSQ-004EX in patients with advanced solid tumors by ORR per RECIST v1.1. This is currently a single-institution study that is actively enrolling/recruiting patients.
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