{
  "abstract": "Background Imneskibart (AU-007) is a mAb binding to interleukin-2 (IL-2) at an epitope that prevents binding to CD25 in the trimeric IL-2 receptor, while allowing engagement with the dimeric receptor, CD122/CD132. Imneskibart bound IL-2 expands T effector (Teff) and NK cell populations (dimeric IL-2R) without expanding regulatory T cells (Tregs; trimeric IL-2R). Avelumab is an anti-PD-L1 mAb containing an active Fc region. Avelumab can block the PD-L1/PD-1 checkpoint, and initiate antibody-dependent cell-mediated cytotoxicity mediated by NK cells, bringing innate and adaptive immunity against tumors.Methods Four ongoing Phase 2 (Ph2) expansion cohorts evaluate 8-week cycles of the recommended Ph2 dose (RP2D) of 9 mg/kg imneskibart IV Q2W + one subcutaneous (SC) 135K IU/kg aldesleukin dose on Day 1. Ph2 Cohort 1 evaluates the RP2D and Cohort 4 evaluates the RP2D-1/RP2D + nivolumab (data immature, not reported), both in melanoma; Cohort 2 evaluates the RP2D and Cohort 3 evaluates the RP2D-1/RP2D + avelumab in PD-L1-positive (≥1%) NSCLC that progressed on anti-PD-1/L1 ± chemotherapy.Results Twelve melanoma patients enrolled in Cohort 1 and two in Ph1 (received below the RP2D). Two melanoma patients refractory to anti-CTLA-4 and anti-PD-1 had tumor reductions of 48% (14 months on treatment) and 100% (continues treatment at 16 months). A patient refractory to anti-PD-1 + anti-LAG-3 had a 58% tumor reduction (continues treatment at 13 months). An acral melanoma patient progressed on anti-CTLA-4 and anti-PD-1 had 12 months stable disease (SD).In NSCLC, of two Cohort 2 patients, one is ongoing with SD at five months. In Cohort 3, six NSCLC patients received avelumab plus the RP2D-1 (four patients; one with 45% target lesion reduction refractory to prior anti-PD-1, two with SD, one pending evaluation) or the RP2D (two patients; one with progressive disease, one pending evaluation).Drug related Grade 3/4 events occurred in 15% of patients receiving imneskibart plus aldesleukin, and the most common Grade 1/2 events occurred in ≤20% of patients.Conclusions Imneskibart + low-dose SC aldesleukin possess a unique mechanism of action by reducing Tregs while increasing the Teff/Treg ratio, resulting in clinically meaningful tumor regressions and a low incidence of Grade 3/4 adverse events. Melanoma patients with primary resistance to prior doublet immune checkpoint inhibitors had durable, deep tumor reductions. Early signals of tumor regression were observed in the newly opened avelumab combination cohort of NSCLC patients progressing on prior anti-PD-1/L1 ± chemotherapy. Updated data, including additional patients, will be presented at the conference.Acknowledgements Avelumab was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).Trial Registration NCT05267626Ethics Approval This study was approved by Monash Health (Australia) HREC/80672/MonH-2021-295282(v2) and Advarra IRB (US) CR00561013. All patients provided informed consent prior to enrollment.",
  "authors": [
    {
      "affiliations": [
        "Sarah Cannon Research Institute, Nashville, TN, USA"
      ],
      "name": "Meredith Mckean"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Monash Health, Clayton, VIC, Australia"
      ],
      "name": "Sophia Frentzas"
    },
    {
      "affiliations": [
        "Carolina BioOncology Institute, PLLC, Huntersville, NC, USA"
      ],
      "name": "John D Powderly"
    },
    {
      "affiliations": [
        "START San Antonio, San Antonio, TX, USA"
      ],
      "name": "Drew Rasco"
    },
    {
      "affiliations": [
        "Austin Health, Heidelberg, VIC, Australia"
      ],
      "name": "Andrew Weickhardt"
    },
    {
      "affiliations": [
        "The Alfred Hospital, Melbourne, VIC, Australia"
      ],
      "name": "Andrew Haydon"
    },
    {
      "affiliations": [
        "University of Sydney Medical School, Sydney, NSW, Australia"
      ],
      "name": "Paul de Souza"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "George R Blumenschein"
    },
    {
      "affiliations": [
        "Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Siwen Hu-Lieskovan"
    },
    {
      "affiliations": [
        "The START Center for Cancer Research, Grand Rapids, MI, USA"
      ],
      "name": "Nehal Lakhani"
    },
    {
      "affiliations": [
        "Southern Oncology Clinical Research Unit, Bedford Park, SA, Australia"
      ],
      "name": "Ganessan Kichenadasse"
    },
    {
      "affiliations": [
        "Western Health, Sunshine Hospital, St Albans, VIC, Australia"
      ],
      "name": "Catherine Oakman"
    },
    {
      "affiliations": [
        "Peninsula and South East Oncology, Frankston, VIC, Australia"
      ],
      "name": "Vinod Ganju"
    },
    {
      "affiliations": [
        "Biolojic Design Inc, Cambridge, MA, USA"
      ],
      "name": "Timothy L Wyant"
    },
    {
      "affiliations": [
        "Aulos Bioscience, Larkspur, CA, USA"
      ],
      "name": "Jenny Tang"
    },
    {
      "affiliations": [
        "Aulos Bioscience, Larkspur, CA, USA"
      ],
      "name": "Lori Richards"
    },
    {
      "affiliations": [
        "Aulos Bioscience, Larkspur, CA, USA"
      ],
      "name": "Aron Knickerbocker"
    },
    {
      "affiliations": [
        "Biolojic Design, Rehovot, Israel"
      ],
      "name": "Inbar Amit"
    },
    {
      "affiliations": [
        "Biolojic Design, Rehovot, Israel"
      ],
      "name": "Yanay Ofran"
    },
    {
      "affiliations": [
        "Aulos Bioscience, San Francisco, CA, USA"
      ],
      "name": "James R Vasselli"
    }
  ],
  "title": "651 Imneskibart, a human monoclonal antibody (mAb) that binds IL-2 and prevents CD25 binding, + low-dose subcutaneous IL-2: phase 2 update on CPI-refractory melanoma and non-small cell lung cancer (NSCLC)",
  "uid": "08efd91e-d33d-55c2-9c2f-a433a249e3a8"
}