{
  "abstract": "Background Invikafusp alfa (STAR0602), a selective, dual T cell agonist targeting Vβ6/10 TCRs, is being evaluated as monotherapy in the Phase 2 expansion of START-001, a multicenter Phase 1/2 trial in patients with tissue-agnostic TMB-H (≥ 10 mut/Mb) and/or microsatellite instability (MSI)-H solid tumors.Methods Ongoing Phase 2 expansion enrolls patients with TMB-H/MSI-H solid tumors to 3 separate cohorts: tissue-agnostic TMB-H or MSI-H, and colorectal cancer. All patients receive recommended Phase 2 dose of 0.08 mg/kg i.v. invikafusp, Q2W. Here we report the first pooled results ever presented for tissue-agnostic, TMB-H patients from Phase 2 and Phase 1 who received optimal biological dose (range 0.08 to 0.12 mg/kg).Results As of 30 June 2025, 47 patients across 17 different TMB-H solid tumors were enrolled: 33% received ≥ 4 lines of prior therapy; 70% received prior immune checkpoint blockade (ICB) and 30% were ICB-naïve because ICB were either not standard of care or not approved for the condition.Of 47 patients, 33 had ≥ 1 post treatment tumor assessment. Overall, invikafusp showed tissue-agnostic, anti-tumor activity (partial response [PR] and tumor regression) in 10 different TMB-H tumor types (table 1). Specifically, 16 patients (49%) had target lesion reduction with 8 (24%) PR and 19 (58%) stable disease (82% disease control) per RECIST. PR and tumor regression were seen in both ICB-resistant (primary and secondary) and ICB-naive patients, suggesting invikafusp’s tissue-agnostic anti-tumor activity is independent of prior ICB treatment.Invikafusp’s overall safety profile was consistent with its mechanism of action (MoA) of selective, dual T cell activation via both TCR and IL-2 co-stimulation. The most common TEAEs were low-grade, well managed with supportive care.Nanostring on 20 paired blood and tumor specimens showed: 1) unequivocal expansion of Vb6/10 T cells post treatment across all tumor types tested, confirming invikafusp’s MoA of selective expansion of in vivo tumor-infiltrating lymphocytes (TILs); 2) significant upregulation of pathways of cytotoxicity, TCR and chemokine signaling, and costimulatory molecules in TILs post treatment; and 3) downregulation of gene expressions of immune suppression (e.g., PD-1 and FOXP3) in TILs of patients with tumor reduction.Conclusions As a first-in-class, dual T cell agonist, invikasfusp showed clinically meaningful anti-tumor activity in TMB-H patients with potential to overcome ICB resistance, offering them a new class of immune-oncology therapeutics. FDA has granted a Fast Track Designation for invikafusp in TMB-H CRC. Phase 2 expansion is ongoing to further investigate the efficacy of invikafusp.Trial Registration NCT05592626Ethics Approval STARt-001 obtained ethics approval, including the following names of the ethics committee(s) or institutional review board(s), the number/ID of the approval(s). In addition,participants gave informed consent before taking part. The list of the names of the ethics committee(s) or institutional review board(s): Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) CEIm HM Hospitales (CT # 2023-505334-10-01) Dana Farber Cancer Institute IRB (22-577) Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) Institutional Review Board/Privacy Board/Memorial Sloan Kettering Cancer Center (23-239) CEIm HM Hospitales (CT # 2023-505334-10-01) WCG IRB (Inst Tracking #: NCT05592626) University of Miami Human Subject Research Office (HSRO) (IBIS# 20231136) NIH Office of IRB Operations (23-5345) AdventHealth Orlando IRB (2052490-3) WCG IRB (Inst Tracking #: STUDY00019146) WCG IRB (Inst. Tracking #: 24-11-7340)Abstract 1316 Table 1Invikafusp showed tissue-agnostic anti-tumor activity (partial responses and tumor regression) in 10 different tumor types with high tumor mutational burden (TMB-H*)*TMB-H defined as ≥ 10 mut/Mb per local testing #n = number of patients",
  "authors": [
    {
      "affiliations": [
        "Gustave Roussy and Paris Saclay University, Villejuif, France"
      ],
      "name": "Aurélien Marabelle"
    },
    {
      "affiliations": [
        "Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain"
      ],
      "name": "Elena Garralda"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Ryan J Sullivan"
    },
    {
      "affiliations": [
        "Institut Bergonié, Bordeaux, France"
      ],
      "name": "Antoine Italiano"
    },
    {
      "affiliations": [
        "Memorial Sloan Kettering Cancer Center, New York, NY, USA"
      ],
      "name": "Claire F Friedman"
    },
    {
      "affiliations": [
        "START Madrid-FJD, Hospital Fundación Jiménez Díaz., Madrid, Spain"
      ],
      "name": "Manuel Pedregal"
    },
    {
      "affiliations": [
        "Ohio State University – James Comprehensive Cancer Center, Columbus, OH, USA"
      ],
      "name": "Kai He"
    },
    {
      "affiliations": [
        "Sylvester Comprehensive Cancer Center/University of Miami Health System, Miami, FL, USA"
      ],
      "name": "Marijo Bilusic"
    },
    {
      "affiliations": [
        "Institut Universitaire du Cancer, Oncopole, Toulouse, France"
      ],
      "name": "Carlos Gomez-Roca"
    },
    {
      "affiliations": [
        "National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
      ],
      "name": "Nicholas P Tschernia"
    },
    {
      "affiliations": [
        "Gustave Roussy and Paris Saclay University, Villejuif, France"
      ],
      "name": "Alberto Hernando Calvo"
    },
    {
      "affiliations": [
        "Gustave Roussy and Paris Saclay University, Villejuif, France"
      ],
      "name": "Matthieu Roulleaux Dugage"
    },
    {
      "affiliations": [
        "Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"
      ],
      "name": "Mercedes Herrera"
    },
    {
      "affiliations": [
        "AdventHealth Medical Group, Orlando, FL, USA"
      ],
      "name": "Guru P Sonpavde"
    },
    {
      "affiliations": [
        "Sarah Cannon Research Institute, Nashville, TN, USA"
      ],
      "name": "Meredith P Pelster"
    },
    {
      "affiliations": [
        "Fred Hutchinson Cancer Center, Seatte, WA, USA"
      ],
      "name": "Diane Tseng"
    },
    {
      "affiliations": [
        "Karmanos Cancer Institute, Detroit, MI, USA"
      ],
      "name": "Wasif Saif"
    },
    {
      "affiliations": [
        "Dana-Farber Cancer Institute, Boston, MA, USA"
      ],
      "name": "Ann W Silk"
    },
    {
      "affiliations": [
        "Marengo Therapeutics, Inc, Cambridge, MA, USA"
      ],
      "name": "Shannon McCue"
    },
    {
      "affiliations": [
        "Marengo Therapeutics, Inc, Cambridge, MA, USA"
      ],
      "name": "Karunya Srinivasan"
    },
    {
      "affiliations": [
        "Marengo Therapeutics, Inc, Cambridge, MA, USA"
      ],
      "name": "Zhen Su"
    },
    {
      "affiliations": [
        "Marengo Therapeutics, Inc, Silver Spring, MD, USA"
      ],
      "name": "Ke Liu"
    },
    {
      "affiliations": [
        "Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"
      ],
      "name": "Lillian L Siu"
    },
    {
      "affiliations": [
        "National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"
      ],
      "name": "James L Gulley"
    }
  ],
  "title": "1316 Initial monotherapy clinical activity of invikafusp alfa, a first-in-class TCR β-chain-targeted bifunctional antibody, in tissue-agnostic, TMB-H patients from STARt-001, a phase 1/2 trial",
  "uid": "23b6ed8f-9c9a-57f0-a168-f26188abab13"
}