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Hong Wang



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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.03-03 - Association Between Molecular Spectrum of EZH2 Variants and Prognosis in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 93)

      08:00 - 18:00  |  Author(s): Hong Wang

      • Abstract

      Background

      Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness in non-small-cell lung cancer (NSCLC) by EZH2 remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EZH2 mutations.

      Method

      A total of 1122 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EZH2 mutations and other genes were detected by next generation sequencing.

      Result

      EZH2 gene mutation rate was 0.62% (7/1122) in non-small cell lung cancer, including K515R (1 patient), I55M (1 patient), D142H (1 patient), K222N (1 patient), Q66R (1 patient), P486S (1 patient), and S652C (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EZH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 16.0 months and 20.0 months respectively (P=0.88); patients with (n=6) or without (n=1) co-occurring TP53 mutations had a median OS of not up to now and 20.0 months respectively (P=0.79); patients with (n=2) or without (n=5) co-occurring BRAF mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.45); patients with (n=2) or without (n=5) co-occurring SMARCA4 mutations had a median OS of 20.0 months and not up to now respectively (P=0.88).

      Conclusion

      EZH2 mutation may predict a worse prognosis of NSCLC. Methyltransferase inhibitor may be beneficial for NSCLC patients with specific EZH2 mutations. EGFR, TP53, BRAF, SMARCA4 gene accompanied may have less correlation with EZH2 mutation in NSCLC patients. The findings of this study could facilitate both clinical trial design and therapeutic strategies.

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.06 - A PII Study of Toripalimab, a PD-1 mAb, in Combination with Chemotherapy in EGFR+ Advanced NSCLC Patients Failed to Prior EGFR TKI Therapies (Now Available) (ID 1160)

      14:00 - 15:30  |  Author(s): Hong Wang

      • Abstract
      • Presentation
      • Slides

      Background

      EGFR TKI is the standard 1st line therapy for the patients (pts) with advanced NSCLC harboring EGFR mutations. While PD-1 checkpoint blockade has become an integral component of disease management for EGFR wild type NSCLC pts at various settings, platinum-based chemotherapy is still the standard of care for EGFR mutated NSCLC pts who progress after EGFR targeting therapy. Early attempts to combine EGFR TKI with checkpoint blockade had resulted in exacerbated immune related toxicity in the lung. Here we aimed to prospectively evaluate toripalimab, a humanized PD-1 mAb approved for 2nd line treatment of melanoma, in combination with chemotherapy to treat EGFR mutated NSCLC pts after failure of EGFR targeting therapy.

      Method

      This is a phase II, multicenter, open-label, single-arm study for pts with EGFR activating mutations who have failed prior EGFR-TKI therapies without T790M mutation or failed osimertinib treatment. Pts were treated with 240mg or 360mg fixed dose toripalimab once every 3 weeks in combination with carboplatin and pemetrexed for up to 6 cycles, followed by toripalimab plus pemetrexed maintenance therapy until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) at week 12 as assessed by investigator per RECIST v1.1 once every 6 weeks. Secondary endpoints were safety, ORR, DOR, DCR, TTR, PFS, OS, PK and immunogenicity.

      Result

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      Forty pts were enrolled from Apr 25, 2018 to March 22, 2019 with 52.5% female pts and a median age of 57.5. 57.5% pts harbored EGFR exon19 deletion while 42.5% pts had exon21 L858R mutation. Only 1 pt had T790M mutation who progressed after osimertinib treatment. In ITT population, 13 confirmed partial response (PR) and 22 stable disease (SD) were observed at week 12 for a 32.5% ORR. As of Jul 25 2019, among 40 pts, 20 confirmed PR and 15 SD were observed for a 50% ORR (95% CI, 33.8% to 66.2%) and an 87.5% DCR (95% CI, 73.2% to 95.8%). Median progression free survival (PFS) was 7.0 months, and median duration of response (DOR) was 7.0 months. Treatment emergent adverse events (TEAE) occurred in 39 (97.5%) of the pts, grade 3 or higher events occurred in 25 (62.5%) of pts including two deaths. Most common AE included leukopenia, neutropenia, thrombocytopenia, anemia, nausea, and loss of appetite. Treatment discontinuation due to AE occurred in 4 (10%) of the pts.

      Conclusion

      Anti-PD-1 mAb, toripalimab in combination with carboplatin and pemetrexed has shown a promising anti-tumor efficacy with a tolerable safety profile for advanced NSCLC patients with EGFR mutated who progressed after EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). A phase III registration study will be initiated in May 2019.

      (Clinical trial information: NCT03513666)

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