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Robert Anton Belderbos



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    OA09 - Mesothelioma from Pathogenesis to Therapy (ID 132)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
    • Presentations: 1
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      OA09.06 - Nivolumab in Recurrent Malignant Pleural Mesothelioma: Real-World Data From Expanded Access Program In The Netherlands (ID 1757)

      15:30 - 16:30  |  Presenting Author(s): Robert Anton Belderbos

      • Abstract
      • Presentation
      • Slides

      Introduction

      Second-line treatment options for patients with recurrent malignant pleural mesothelioma (MPM) after first line chemotherapy are lacking. Nivolumab, an anti-PD-1 monoclonal antibody, showed promising results in phase II trials in pre-treated MPM patients. Data from the PROMISE-meso randomized phase III trial (NCT02991482), however, failed to show superiority of pembrolizumab (anti-PD-1) over chemotherapy in second line treatment. The aim of our study was to describe the clinical outcome of pre-treated MPM patients receiving nivolumab in a real-world setting and potentially identify a subgroup of patients that do benefit from anti-PD-1 treatment through extensive analysis of clinical and peripheral blood parameters.

      Methods

      Since October 2017, patients with MPM received nivolumab in the BMS-sponsored Expanded Access Program (EAP). Patients were eligible if they had progressive disease after at least one line of chemotherapy; a good clinical performance score at time of screening (ECOG 0-1); adequate lab values; no autoimmune disease and no treatment with systemic steroids (>10 mg/day prednisone equivalents). In the Erasmus Medical Center and The Netherlands Cancer Institute, patients were treated biweekly with nivolumab 3mg/kg independent of PD-L1 expression. CT scan evaluation was performed every 6-12 weeks, using modified RECIST for malignant mesothelioma supplemented with the immune RECIST criteria regarding pseudoprogression and confirmation of response.

      Results

      At the WCLC 2020, data of the Erasmus cohort with addition of the NCI cohort, accounting for 107 patients will be presented. This will include the results of 59 patients treated with nivolumab at the Erasmus MC that were presented at the WCLC 2019 (MA05.09). In the full cohort, the median progression-free survival (mPFS) was 2.3 months (95% CI: 1.6-2.9) and the median overall survival (mOS) was 6.7 (95% CI: 6.2-10.0) months. After 12 weeks, the disease control rate (DCR) was 37% and the objective response rate (ORR) was 10%. PD-L1 status was determined in 33 patients (30%) and PD-L1 positivity (≥1%) was associated with an improved ORR (36% vs 9%, p-value 0.05), but not with PFS or OS. Low albumin was associated with worse OS (p-value 0.002). Median OS was significantly longer for patients who had partial response to treatment (p-value 0.0002). Remarkably, with a median follow up of 14.1 months in the group of patients with PR (n=10), no deaths were reported and only 2 patients progressed.

      Conclusion

      In this real-world analysis, ORR and mOS were lower compared to those obtained in phase II and III trials with checkpoint inhibitors. However, exceptional survival rates were observed in patients who had a radiological response. PD-L1 expression and albumin were associated with greater response rate and may represent useful biomarkers for nivolumab treatment in MPM.

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    P24 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Mesothelioma Clinical and Trials in Progress (ID 138)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 01:00, ePoster Hall
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      P24.03 - A Multicenter Randomized Phase III Trial of Dendritic Cell Maintenance Therapy After Chemotherapy in Mesothelioma; Denim Trial (ID 1784)

      00:00 - 01:00  |  Presenting Author(s): Robert Anton Belderbos

      • Abstract
      • Slides

      Introduction

      Malignant Pleural Mesothelioma (MPM) is an aggressive, and lethal cancer. Current treatment first line treatment, consisting of a combination of antifolate and platinum-based chemotherapy, results in an overall survival of 9-15 months. There are no approved maintenance therapies and no treatment has yet shown improved survival in the relapsed setting. Immune checkpoint inhibition exhibits some clinical activity suggesting that adaptive immunity may be harnessed for effective therapy. However mesotheliomas exhibit low numbers of tumor-infiltrating CD8+ T-cells. Dendritic cell (DC) therapy can be therapeutically harnessed to instigate an immune response and activate tumor-specific CD8+ T-cells. Allogenic tumor-lysate loaded DC therapy has proven to be effective in mice and is both safe and feasible in patients. We have therefore initiated a European multicenter, open label randomized, phase 2/3 trial to examine the efficacy of DC therapy in patients with histologically proven MPM.

      Methods

      In this open-label, multicenter phase III trial patients are randomized after first line chemotherapy treatment to receive either DC therapy plus Best Supportive Care (BSC) or BSC only according to the discretion of the local investigator after first line chemotherapy treatment. The primary end point is overall survival. The secondary endpoints will be safety and tolerability, progression-free survival , overall response rate and quality of life. Immunomonitoring will be done as part of the exploratory analysis. 230 patients are planned to be enrolled in the trial. Study enrollment started in May 2018 and inclusion is expected to be completed in the last quartile of 2020. The independent data safety monitoring board last reviewed the trial in September 2019 and suggested that the trial continues as planned. A new futility analysis is planned in the spring of 2020.

      Conclusion

      This Phase III trial will determine whether DC therapy in patients with MPM can improve clinical outcomes as a maintenance treatment after chemotherapy to provide a new treatment option for MPM.

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