{
  "abstract": "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’ CRISPR 2® 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 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 assesses 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 one to three 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 one 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 6-12 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.Ethics Approval This study will be conducted in accordance with the protocol, all regulatory requirements as stated in state, local and federal regulations; as well as institutional policies, including: • ICH Harmonized Tripartite Guidelines for Good Clinical Practice 1996. • US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 56 concerning informed consent and IRB regulations). • Declaration of Helsinki, concerning medical research in humans (Recommendations Guiding Physicians in Biomedical Research Involving Human Patients, Helsinki 1964, amended Tokyo 1975, Venice 1983, Hong Kong 1989, Somerset West 1996). The Investigator agrees to adhere to the instructions and procedures described in it and thereby to adhere to the principles of GCP. The protocol, ICF(s), and any participant materials will be submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) must be obtained before any participant is consented.",
  "authors": [
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Rodabe Amaria"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Khaled Sanber"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "George R Blumenschein"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Mehmet Altan"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Maria Pia Morelli"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Amir A Jazaeri"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Scott Kopetz"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Michael Davies"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Steffy Jose"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Santresa Turner"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Isabella C Glitza"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Alexandra P Ikeguchi"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Jennifer L McQuade"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Hussein A Tawbi"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Cara L Haymaker"
    },
    {
      "affiliations": [
        "Cell Therapy Manufacturing Center, Houston, TX, USA"
      ],
      "name": "Chantale Bernatchez"
    },
    {
      "affiliations": [
        "Cell Therapy Manufacturing Center, Houston, TX, USA"
      ],
      "name": "Marie Andree Forget"
    },
    {
      "affiliations": [
        "KSQ Therapeutics, Inc, Lexington, MA, USA"
      ],
      "name": "Karrie K Wong"
    },
    {
      "affiliations": [
        "KSQ Therapeutics, Inc, Lexington, MA, USA"
      ],
      "name": "Erica R Tobin"
    },
    {
      "affiliations": [
        "KSQ Therapeutics, Inc, Lexington, MA, USA"
      ],
      "name": "Micah J Benson"
    },
    {
      "affiliations": [
        "KSQ Therapeutics, Inc, Lexington, MA, USA"
      ],
      "name": "Anna Truppel-Hartmann"
    },
    {
      "affiliations": [
        "KSQ Therapeutics, Inc, Lexington, MA, USA"
      ],
      "name": "Patricia M Harris"
    }
  ],
  "title": "569 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",
  "uid": "68ab4064-d518-5a3c-909f-056b266c6ef3"
}