{
  "abstract": "Background Despite transformative advances with immunotherapies, most patients with solid tumors do not achieve durable responses. Tumors evade immunity through multiple mechanisms; thus, therapies that engage diverse arms of the immune response and the tumor directly are needed. Invariant Natural Killer T (iNKT) cells are uniquely positioned to address this challenge, combining direct tumor cell killing with the ability to activate host immunity and remodel the suppressive tumor microenvironment. agenT-797, a scalable, allogeneic, off-the-shelf iNKT cell therapy expanded from healthy donors, can be administered without HLA matching or lymphodepletion. AgenT-797 has shown broad clinical benefit and synergy with PD-1 blockage. Here, we present updated clinical and translational findings from a Phase 1 trial evaluating agenT-797 ± anti-PD-1 in patients with solid tumors.Methods A Phase 1 ( NCT05108623), open-label study evaluated the safety, tolerability, and preliminary clinical activity of agenT-797 in participants with relapsed/refractory solid tumors and aimed to define the recommended Phase 2 dose. AgenT-797 was administered as a single intravenous infusion using a 3+3 dose-escalation design (n=34). The study also assessed the safety and activity of agenT-797 in combination with approved anti-PD-1 immune checkpoint inhibitors, in the same patient population (n=6).Results Single administration of agenT-797 demonstrated clinical activity in heavily pre-treated solid tumor patients, and updated clinical data will be shared. Notably, a patient with metastatic testicular cancer treated with agenT-797 and anti-PD-1 achieved complete clinical, radiologic, and biochemical remission, with no evidence of disease more than two years later, despite prior failure of platinum-based chemotherapy, autologous stem cell transplant, and multiple ICIs (anti-PD-1, anti-CTLA-4, anti-TIGIT). In addition, a confirmed partial response was observed in a patient with gastric cancer treated with 2 lines of therapy. Beyond these landmark cases, nine patients with PD-1-refractory cancers (NSCLC, appendiceal, and testicular tumors) achieved disease stabilization. AgenT-797 was well tolerated as monotherapy and in combination with PD-1 blockade, with no new safety signals. These findings underscore the potential of agenT-797 to deliver durable clinical benefit in patients with advanced, treatment-resistant solid tumors. Additional patients with exceptional long-term benefit will be described.Conclusions AgenT-797 is a multifunctional and well-tolerated treatment modality for the treatment of cancer. This Phase I trial data demonstrates clinical activity in patients with solid tumors, with a number of durable responses. This data supports the potential of agenT-797 in solid tumors. MiNK Therapeutics are currently evaluating agenT-797 in a Phase 2 trial in patients with gastric cancer.Acknowledgements We are deeply grateful to the patients and their families for their participation in this clinical trial.Trial Registration NCT05108623Ethics Approval Institutional Review Board (IRB) approval was obtained at each participating site, and all patients provided written informed consent prior to enrollment.",
  "authors": [
    {
      "affiliations": [
        "MiNK Therapeutics, Lexington, MA, USA"
      ],
      "name": "Marco A Purbhoo"
    },
    {
      "affiliations": [
        "MiNK Therapeutics, Lexington, MA, USA"
      ],
      "name": "Thiago Favano"
    },
    {
      "affiliations": [
        "Sarah Cannon Research Institute, Nashville, TN, USA"
      ],
      "name": "Benjamin Garmezy"
    },
    {
      "affiliations": [
        "Norton Cancer Institute, Louisville, KY, USA"
      ],
      "name": "John Hamm"
    },
    {
      "affiliations": [
        "Legorreta Cancer Center at Brown University, Providence, RI, USA"
      ],
      "name": "Benedito A Carneiro"
    },
    {
      "affiliations": [
        "University of Cincinnati Cancer Center, Cincinnati, OH, USA"
      ],
      "name": "Trisha M Wise-Draper"
    },
    {
      "affiliations": [
        "University of Colorado Cancer Center, Aurora, CO, USA"
      ],
      "name": "Breelyn Wilky"
    },
    {
      "affiliations": [
        "Earle A. Chiles Research Institute, Portland, OR, USA"
      ],
      "name": "Rachel E Sanborn"
    },
    {
      "affiliations": [
        "USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA"
      ],
      "name": "Anthony El-Khoueiry"
    },
    {
      "affiliations": [
        "MiNK Therapeutics, Lexington, MA, USA"
      ],
      "name": "Marc Van Dijk"
    },
    {
      "affiliations": [
        "MiNK Therapeutics, Lexington, MA, USA"
      ],
      "name": "Nils-Petter Rudqvist"
    },
    {
      "affiliations": [
        "MiNK Therapeutics, Lexington, MA, USA"
      ],
      "name": "Jennifer S Buell"
    }
  ],
  "title": "1344 AgenT-797, an allogeneic iNKT cell therapy, demonstrates durable clinical activity in solid tumors: updated phase 1 findings",
  "uid": "459e6707-0d2c-5bc8-a2e3-6c6756561940"
}