{
  "abstract": "Background Colorectal cancer with liver metastases and no mismatch repair defect (mCRC-MSS) is refractory to immune checkpoint inhibitors. Trans-arterial chemoembolization (TACE) and radioembolization (TARE) could be used but with limited survival advantage. We studied trans-arterial tirapazamine embolization (TATE) in mCRC-MSS and investigated whether tumor necrosis induced by TATE could enhance the efficacy of pembrolizumab (pembro).Methods Subjects with mCRC-MSS who had progressed on 2+ lines of chemotherapy and suitable for embolization were enrolled in two studies ( NCT03259867 and NCT04701476) and pooled for analysis. Treatment consisted of IV administration of pembro every 3 weeks starting day 1 until progression or death. TATE was performed on day 8 and repeated every 3-4 weeks for up to 4 treatments for tumor debulking. Efficacy was evaluated by RECIST and mRECIST, and safety by CTCAE v5. Primary endpoint was Overall Response Rate (ORR) per RECIST. Secondary endpoints included ORR per mRECIST, Overall Survival (OS), Progression Free Survival (PFS), Disease Control Rate (DCR), and abscopal effect of TATE in extra-hepatic lesions.Results 29 mCRC patients (Male/Female=17/12, Median age 56, and range 31-80) were enrolled in 2 sites (22 in UC Irvine Medical Center, 7 in China Medical University, Hsinchu Hospital in Taiwan). All subjects were Microsatellite Stable (MSS). 19 (65.5%) had an ECOG 0, and 10 (34.5%) had ECOG 1. All received at least 2 lines, and 20 (69%) had 4 or more lines of chemotherapy. 10 received prior surgical resection, 9 received thermal ablation, and 3 received either prior TARE or TACE. 9 (32.1%) had bilobar disease, and 15 (53.5%) with lung metastases. Median number of TATE treatments was 1, maximal 4. 17 patients had mRECIST analysis and revealed 1CR/3PR or ORR 4/29 (13.8%), DCR (CR+PR+SD) 9/29 (31.0%), and PFS 3.2 months. 24 were analyzed by RECIST and showed 2PR or ORR 2/29 (6.9%), and DCR 12/29 (41.4%). There were 23 death events and 6 subjects were censored. Median OS was 11.5 months with 1 year survival rate 46%. Two patients had extra-hepatic lesions consisting of lung metastasis and/or lymph nodes demonstrated a response to pembro since extra-hepatic disease is not embolized ( figure 1). The most common adverse events were nausea, transient elevation of AST and ALT, consistent with safety profile of TATE.Conclusions Combination of TATE with pembro shows promising efficacy for treatment refractory mCRC with an acceptable safety profile. A follow-up randomized control trial is underway to assess efficacy compared to standard of care chemotherapy.Acknowledgements Funding was supported by Teclison, Inc.Trial Registration NCT03259867, NCT04701476Ethics Approval Ethics approval was obstained by the IRB of each participating hospitals, including UC-Irvine Medical Center, CA, USA (UCI IRB HS#2017-3393, UCI 16-94); Chinese Medical College, Taiwan; Triservice General Hospital, Taiwan.Abstract 492 Figure 1Abscopal effect in lung lesions after metastatic liver lesions were treated with TATE",
  "authors": [
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Ricardo Azevedo"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Jason Zell"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Farshid Dayyani"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Jennifer Valerin"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Fa-chyi Lee"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Dayantha Fernando"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "David K Imagawa"
    },
    {
      "affiliations": [
        "Chinese Medical University, Hsin Chu, Taiwan, Taiwan"
      ],
      "name": "Chih-yuan Chung"
    },
    {
      "affiliations": [
        "Chinese Medical University, Hsin Chu, Taiwan, Taiwan"
      ],
      "name": "Chang-hsien Liu"
    },
    {
      "affiliations": [
        "University of California, Irvine, Orange, CA, USA"
      ],
      "name": "Nadine Abi-Jaoudeh"
    }
  ],
  "title": "492 Phase 2 single-arm study of trans-arterial tirapazamine embolization (TATE) plus pembrolizumab for liver metastatic colorectal cancer who have progressed on at least two lines of chemotherapy",
  "uid": "17d4a8a9-b0da-57f8-a877-d3492fa26d3c"
}