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H. Zhen



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    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03a-014 - A Dose-Finding and Phase 2 Study of Ruxolitinib plus Pemetrexed/Cisplatin for Nonsquamous Non–Small Cell Lung Cancer (NSCLC) (ID 3874)

      14:30 - 14:30  |  Author(s): H. Zhen

      • Abstract

      Background:
      Dysregulation of the JAK/STAT pathway contributes to abnormal inflammatory responses, oncogenesis, treatment resistance, and poor prognosis in NSCLC. This phase 2 clinical trial evaluated the JAK1/JAK2 inhibitor ruxolitinib+pemetrexed/cisplatin as first-line treatment for patients with stage IIIB/IV or recurrent nonsquamous NSCLC and systemic inflammation (per modified Glasgow Prognostic Score [mGPS]).

      Methods:
      Key inclusion criteria were mGPS of 1/2 and ECOG performance status ≤1. Part 1, an open-label, 21-day safety run-in, assessed ruxolitinib (15 mg BID [chosen dose for Part 2]) plus pemetrexed (500 mg/m[2] IV on Day 1) and cisplatin (75 mg/m[2] IV on Day 1). Ruxolitinib dose selection for Part 2 required <3 dose-limiting toxicities (DLTs) for 9 evaluable patients. Part 2 randomized patients to ruxolitinib+pemetrexed/cisplatin or placebo+pemetrexed/cisplatin. The trial was terminated early for lack of efficacy in other solid tumor programs in patients with high systemic inflammation.

      Results:
      All 15 patients enrolled in Part 1 received ruxolitinib 15 mg BID plus pemetrexed/cisplatin. Median age was 64 years; male, 80%; mGPS 1, 80%. Median treatment duration was 140 days. The Table reports Part 1 safety data. Four patients were inevaluable for DLTs (<80% compliance, n=2; disease progression, n=2). No DLTs occurred in 11 evaluable patients. The Part 1 overall response rate (ORR) was 53% (8/15; all partial responses). At study termination, 39 and 37 patients were randomized in Part 2 to ruxolitinib and placebo, respectively. Median treatment duration was 43 days. ORR was 31% (12/39) with ruxolitinib+pemetrexed/cisplatin versus 35% (13/37) with placebo+pemetrexed/cisplatin (all partial responses). The short follow-up duration may limit interpretation of Part 2 efficacy. The Part 2 safety profile was consistent with Part 1 (data to be presented).

      Table. The Most Common Treatment-Emergent Adverse Events in Part 1
      Ruxolitinib+Pemetrexed/Cisplatin (N=15)
      Event, n (%) All-Grade Grade 3/4
      Nonhematologic*
      Nausea 11(73) 1(7)
      Fatigue 8(53) 3(20)
      Vomiting 8(53) 1(7)
      Constipation 7(47) 0
      Diarrhea 7(47) 0
      Dizziness 7(47) 0
      Peripheral edema 7(47) 0
      Decreased appetite 6(40) 0
      Pyrexia 6(40) 0
      Dyspnea 5(33) 1(7)
      Pneumonia 4(27) 3(20)
      Pulmonary embolism 2(13) 2(13)
      Sepsis 2(13) 2(13)
      New/worsening hematologic laboratory abnormalities
      Anemia 13(87) 5(33)
      Lymphopenia 11(73) 2(13)
      Leukopenia 9(60) 1(7)
      Neutropenia 9(60) 5(33)
      Thrombocytopenia 9(60) 1(7)
      *Common all-grade (≥30%) or grade 3/4 (≥10%) events.

      Conclusion:
      Ruxolitinib 15 mg BID had an acceptable safety profile in combination with pemetrexed/cisplatin as first-line treatment of patients with stage IIIB/IV or recurrent nonsquamous NSCLC.