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Mateusz Opyrchal



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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.01 - Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy (ID 12922)

      13:30 - 13:40  |  Author(s): Mateusz Opyrchal

      • Abstract
      • Presentation
      • Slides

      Background

      Treatment options are limited for lung cancer patients whose disease has progressed on anti-PD-(L)1 therapy. HDAC inhibitors may synergize with PD-(L)1 inhibition to overcome resistance. We report the interim results of a Phase 2 trial of entinostat (ENT), a class I selective histone deacetylase (HDAC) inhibitor, plus pembrolizumab (PEMBRO) in patients with NSCLC previously treated with anti-PD-(L)1 therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      ENCORE-601 is an open-label study evaluating the combination of ENT + PEMBRO in patients with recurrent or metastatic NSCLC and prior progression on anti-PD-1/PD-L1 therapy. Patients were eligible irrespective of histology or baseline PD-L1 expression. Patients were treated with ENT 5 mg PO weekly and PEMBRO 200 mg IV Q3W. The primary endpoint was ORR as assessed by irRECIST. Tumor biopsies and blood samples for immune correlates were taken prior to and during treatment in a subset of patients. A total of 70 patients will be enrolled.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 57 patients with anti-PD-(L)1 resistant/refractory NSCLC, the confirmed objective response rate with ENT + PEMBRO was 11% (6 of 57, 95% CI: 4-21%). Of 49 patients with post-baseline tumor measurements, 47% had at least some reduction in tumor. Anti-PD-(L)1 therapy was the most recent line of therapy in 38 of 57 patients, and the median time from last dose of prior anti-PD-(L)1 to study entry was 67 days. The median duration of response with ENT + PEMBRO was 5 months, with the longest over 14 months. Of the 6 responders, four were PD-L1 negative at study entry. Response was associated with a higher median baseline level of peripheral classical monocytes (CD14+CD16-HLA-DRhi) with 16.9% of total live PBMCs in responders (n=6) compared to 8.2% in non-responders (n=45). 5 patients (8.8%) experienced Grade 3/4 related irAEs (2 events each of pneumonitis and colitis, 1 event of hyperthyroidism). In addition, 19 patients (33.3%) experienced other Grade 3/4 related AEs with only fatigue, anemia, hypophosphatemia, and hyponatremia occurring in more than 1 patient. Additional correlative analyses to identify biomarkers of response, including whole exome sequencing and RNAseq, are in progress.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ENT + PEMBRO demonstrated anti-tumor activity and acceptable safety in patients with NSCLC who have progressed on prior PD-(L)1 blockade. Ongoing analysis of immune correlates may identify strategies for effective patient selection.

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-26 - Interim Results from a Phase I/II Trial of Nivolumab in Combination with CIMAvax-EGF as Second-Line Therapy in Advanced NSCLC (ID 13359)

      16:45 - 18:00  |  Author(s): Mateusz Opyrchal

      • Abstract

      Background

      CIMAvax-EGF (CE), a recombinant anti-human epidermal growth factor (EGF) vaccine, has demonstrated survival benefit as maintenance therapy in advanced NSCLC. We report the results from the dose-escalation phase I portion of the study investigating CE in combination with Nivolumab(N) in patients (pts) with advanced stage, previously treated immunotherapy-naïve NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is an open-label phase I dose-escalation study with a 3+3 design. Intramuscular CE is investigated in two dose levels (1.2 and 2.4 mg, given q 2 weeks x 4 doses during the induction phase, then q monthly during the maintenance phase) in combination with 240 mg iv N q 2 weeks. Pts remain on treatment until disease progression, serious toxicity or consent withdrawal. The primary objective is to determine the safety and recommended phase II dose (RP2D) of CE in combination with N. Secondary objectives include tumor response and correlative markers of immune response. Toxicities are graded according to CTCAE v4.03. No intra-pt dose escalation is allowed

      4c3880bb027f159e801041b1021e88e8 Result

      9 pts have completed DLT assessments (7Female: 2Male). Median age is 58 (range 46-69). All pts have EGFR, KRAS and ALK wildtype NSCLC. Adenocarcinoma is the predominant histologic subtype (7/9). One pt had Gr 3 myocarditis (LVEF 25%-30%) attributed to N alone on Cycle 1 day 8 and taken off study. LVEF improved (60%-65%) but pt eventually had Gr 5 brain hemorrhage due to brain metastasis, unrelated to treatment, on Cycle 1 day 29. No other treatment-related CTC grade 3+ AEs attributed to either N and/or CE. The RP2D dose was established at 2.4 mg for CE. Objective response rate of 44% was seen (4 PRs: 3 adenocarcinoma, 1 squamous; 3 PD-L1 <1%, 1 PD-L1 60%). There is a significant inverse correlation (p<0.001) between the temporal change in anti-EGF Ab titers and the change in serum EGF levels based upon a generalized linear model. 71% of pts (95% CI 36%-92%) achieved an anti-EGF Ab titer of > 1:4000 after 3 vaccine doses by day 43. We will present additional information on safety, efficacy profile and correlative data in the meeting

      8eea62084ca7e541d918e823422bd82e Conclusion

      Combination of N+CE did not show unexpected toxicities. Preliminary efficacy and immunological data warrant further investigation.

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