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Robin Cornelissen



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    MA11 - Expanding Targetable Genetic Alterations in NSCLC (ID 251)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
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      MA11.04 - Updated Efficacy, Safety and Dosing Management of Poziotinib in Previously Treated EGFR and HER2 Exon 20 NSCLC Patients (ID 1630)

      14:15 - 15:15  |  Presenting Author(s): Robin Cornelissen

      • Abstract
      • Slides

      Introduction

      Management of non-small cell lung cancer (NSCLC) with EGFR or HER2 exon 20 mutations is an unmet medical need. Poziotinib, a potent, irreversible, tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 mutations, is being studied in a multi-cohort, multicenter, Phase 2 study (ZENITH20). Here, we present updated efficacy results across subgroups of NSCLC patients with EGFR and HER2 exon 20 insertion mutations. Topline results for 2nd line EGFR and HER2 cohorts (ZENITH20-1 and -2) were presented previously.

      Methods

      Patients enrolled in ZENITH20 had EGFR or HER2 exon 20 insertion mutations per a CLIA certified (or equivalent) NGS test. Poziotinib (16 mg) was administered orally, once daily (QD), and dose interruptions/reductions were allowed for toxicity if needed. The endpoints were objective response rate (ORR), progression-free-survival, and duration of response (DOR) as evaluated by a central, independent image review committee using RECIST 1.1.

      Results

      In this ongoing study, 205 patients were enrolled in first 2 cohorts (115 2nd line EGFR and 90 2nd line HER2 respectively) and the enrollment is ongoing in the remaining cohorts. Patients had a median age of 61 years, 66% were females, 67% were non-smokers, and 13% had concurrent stable brain metastases at entry. Median number of prior therapies was 2 (range, 1 – 9). 94% of patients had prior chemo/platinum-based therapy; 65% immunotherapy, including checkpoint inhibitors; 28% monoclonal antibodies; 20% TKI therapy. The most common treatment-related Grade ≥3 AEs were rash (29%), diarrhea (26%), and mucosal inflammation (10%). The onset of most related AEs occurred in Cycle 1 resulting in 87% dose interruptions and 72% dose reductions. 14% had permanent drug discontinuation for related AEs.

      ORRs in the As-Treated patients were 14.8%/27.8% in EGFR/HER2 with median DORs of 7.4 and 5.1 months, respectively. In the Evaluable patient population, ORRs were 18.3%/35.1% respectively. Consistent responses were seen in patients with multiple lines of prior therapy in both cohorts with ORRs of 15%, 16% in EGFR and 30%, 39% in HER2 for 2+, 3+ lines of therapy respectively. Similar responses were observed across various prior therapy types. Additional analysis of efficacy will be provided for mutation status and CNS activity in both cohorts.

      Conclusion

      Clinical activity was observed in previously treated patiens in both NSCLC EGFR or HER2 exon 20 mutations regardless of specific mutations and prior therapy with consistent responses seen in more heavily pre-treated patients. The safety data shows a manageable toxicity profile that is typical of 2nd generation TKIs. Additional cohorts are enrolling with alternative dose levels and BID dosing.

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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  |  Author(s): Robin Cornelissen

      • 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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