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S.M. Arnold



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    P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      P2.07-008 - CTC 11-001: PhI Study of Carfilzomib (C) + Irinotecan (I) in Relapsed, Irinotecan Sensitive Solid Tumors (ID 241)

      09:30 - 17:00  |  Author(s): S.M. Arnold

      • Abstract
      • Slides

      Background:
      Inactivation of proteasome function allows for increased apoptosis and the potential for enhanced antitumor effect by chemotherapy. Carfilzomib (C) and Irinotecan (I) potentially synergize by increasing camptothecin-induced apoptosis and interfering with topoisomerase-I degradation, preventing DNA damage repair. This report describes the initial phase I study of C + I in adults with relapsed, irinotecan-sensitive cancers including small cell lung cancer (SCLC).

      Methods:
      The primary endpoint was determination of the MTD of 28-day cycle 1 of I (D1,8,15) and C (D1,2,8,9,15,16) using a standard 3+3 Ph1 design. Toxicity and response were evaluated using NCI CTCAE (v4) and RECIST (v1.1). Pharmacodynamics endpoints (proteasome activity, topo-1 expression, and gamma-H2AX protein expression in PBMC) were assessed on C1D1 and C1D2.

      Results:
      16 patients were enrolled at 3 dose levels of C (mg/m2/d) using stepped-up dosing: 20 mg given C1D1 & C1D2 then increased to the dose indicated: 20/27 (N=4), 20/36 (N=9), 20/45 (N=3) and I dosed at 125 mg/m2d. Median age: 64 (range 56-78), 8 M/8F. Tumor types included: SCLC (N=13), non-small cell lung cancer (NSCLC) (N=2) and ovarian (N=1). 6 subjects completed 2 or more cycles of therapy, 4 subjects were not evaluable for dose-limiting toxicity (DLT) secondary to rapid progressive disease (PD) or withdrawal and were replaced. 2 DLTs were observed in cohort 3, Grade (Gr)4 thrombocytopenia lasting ≥ 7 days and Gr3 diarrhea lasting ≥ 7 days) and 1 DLT in cohort 2 (Gr3 diarrhea lasting > 7 days). Serious adverse events (SAEs) by dose level: 20/27: Gr3 Dysphagia and recurrent laryngeal nerve palsy, (unrelated); Gr3 peripheral motor neuropathy and Gr3 urinary incontinence, (unrelated); 20/36: Gr3 fatigue, multiple occurrences; Gr3 diarrhea with dehydration; Gr3 cholelithiasis with dehydration (unrelated); 20/45: Gr3 dehydration, Gr3 anemia, Gr2 anemia and Gr3 acute on chronic kidney disease. Common Gr3/4 AEs were: fatigue (19%), thrombocytopenia (19%), diarrhea (13%), anemia (6%), neutropenia (6%), and leukopenia (6%). One patient (25%), five patients (55%), and two patients (67%) experienced Gr3/4 AEs in cohorts 1, 2, and 3, respectively. The maximum tolerated dose was exceeded at 20/45. Antitumor activity (stable disease or better) was observed in 3 SCLC subjects to date, with updated follow-up to be reported.

      Conclusion:
      C and I is a well-tolerated combination with anti-tumor activity in heavily pretreated patients. The recommended phase 2 dose of Carfilzomib is 20/36 mg/m2/d in combination with Irinotecan 125 mg/m2/d. A phase 2 study in SCLC is ongoing through the Lung Cancer Research Team (LCRT). This study was supported by Onyx Pharmaceuticals, a subsidiary of Amgen Corporation. Clinical trial information: NCT01941316.

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    PLEN 04 - Presidential Symposium Including Top 4 Abstracts (ID 86)

    • Event: WCLC 2015
    • Type: Plenary
    • Track: Plenary
    • Presentations: 1
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      PLEN04.01 - A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): SWOG S0819 (ID 3612)

      10:45 - 12:15  |  Author(s): S.M. Arnold

      • Abstract
      • Presentation
      • Slides

      Background:
      This abstract is under embargo until September 9, 2015 and will be distributed onsite on September 9 in a Late Breaking Abstract Supplement.

      Methods:


      Results:


      Conclusion:


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