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I. Puzanov



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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-062 - PIVOT-02: Phase 1/2 Study of NKTR‐214 and Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumor Malignancies (ID 9130)

      09:30 - 09:30  |  Author(s): I. Puzanov

      • Abstract
      • Slides

      Background:
      Abundance and functional quality of tumor infiltrating lymphocytes are positively linked with tumor response and improved survival with checkpoint inhibitors. NKTR-214 is a CD122-biased agonist that targets the IL2 pathway and is designed to provide sustained signaling through the heterodimeric IL2 receptor pathway (IL2Rβɣ) to preferentially activate and expand NK and effector CD8+ T cells over CD4+ T regulatory cells within the tumor microenvironment. NKTR‐214 is administered on an outpatient basis as a 15-minute IV infusion and has been administered to 28 patients with advanced solid tumors. Single-agent NKTR-214 demonstrates a substantial increase in both CD8+ T and NK cells within the tumor microenvironment in those patients with prior immune checkpoint therapy (Bernatchez et al, SITC poster 2016). Given the favorable safety profile and strong biomarker data, a trial combining NKTR‐214 and nivolumab was initiated.

      Method:
      PIVOT‐02 is a phase 1/2 open‐label trial in patients with locally advanced or metastatic melanoma (MM), non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), urothelial carcinoma, or triple‐negative breast cancer (TNBC). Approximately 250 patients will be enrolled across 5 tumor types and 8 indications, with 26-38 patients per indication. Patients who are immunotherapy naïve will be studied for all 5 tumor types. MM, RCC, or NSCLC patients who are relapse/refractory on one prior anti-PD-1/PD-L1 containing regimen will be studied separately. The primary objectives are to evaluate safety and tolerability, determine the recommended phase 2 dose (RP2D), and assess tumor response by RECIST 1.1. The dose-escalation portion of the trial has enrolled 23 patients (MM= 8, RCC= 11, NSCLC=4), in 5 different cohorts including NKTR-214 at 0.003 (q2w), 0.006 (q2w or q3w), or 0.009 (q3w) mg/kg in combination with a flat dose of nivolumab at 240 (q2w) or 360 (q3w) mg. Extensive blood and tumor tissue samples are being collected in both escalation and expansion phase to measure immune activation using immunophenotyping including flow cytometry, immunohistochemistry (IHC), T-cell clonality and gene expression analyses. Based on safety/tolerability, PK/PD and early biomarker data, the recommended phase 2 dose of NKTR-214 is 0.006 mg/kg q3w with nivolumab 360 mg q3w. The expansion phase of the study is now open for accrual.

      Result:
      Section not applicable

      Conclusion:
      Section not applicable

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