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420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study
  1. Adi Diab1,
  2. Scott Tykodi2,
  3. Gregory Daniels3,
  4. Michele Maio4,
  5. Brendan Curti5,
  6. Karl Lewis6,
  7. Sekwon Jang7,
  8. Ewa Kalinka8,
  9. Igor Puzanov9,
  10. Alexander Spira10,
  11. Daniel Cho11,
  12. Shanhong Guan12,
  13. Erika Puente12,
  14. Ute Hoch12,
  15. Sue Currie12,
  16. Tuan Nguyen12,
  17. Wei Lin12,
  18. Mary Tagliaferri12,
  19. Jonathan Zalevsky12,
  20. Mario Sznol13 and
  21. Michael Hurwitz13
  1. 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  3. 3University of California, La Jolla, CA, USA
  4. 4Azienda Ospedaliera Universitaria Senese, Siena, Italy
  5. 5Providence Cancer Center and Earle A. Chiles Research Institute, Portland, OR, USA
  6. 6University of Colorado, Aurora, CO, USA
  7. 7Inova Fairfax Hospital, Fairfax, VA, USA
  8. 8Santa Familia Medical Institute, Lodz, Poland
  9. 9Roswell Park Cancer Institute, Buffalo, NY, USA
  10. 10Virginia Cancer Specialists, Fairfax, VA, USA
  11. 11NYU Medical Oncology Associates, New York, NY, USA
  12. 12Nektar Therapeutics, San Francisco, CA, USA
  13. 13Yale School of Medicine, New Haven, CT, USA


Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial (NCT02983045),1 leading to FDA Breakthrough Therapy Designation. We present updated clinical results from PIVOT-02 in first-line metMEL, and biomarkers of response.

Methods 41 patients with previously untreated stage IV melanoma (known PD-L1 status by immunohistochemistry; 28–8 PharmDx) received ≥1 dose of BEMPEG(0.006 mg/kg) plus NIVO(360 mg) q3wks; 38 patients were efficacy-evaluable (≥1 post-baseline tumor scan). Primary endpoints were safety and objective response rate (ORR; RECIST v1.1; BICR); other endpoints included PFS, OS and biomarkers. Polyfunctional strength index (PSI) of circulating lymphocytes (determined using single-cell cytokine analysis [Isoplexis]) and eosinophil count (determined from hematology analysis) at baseline and Cycle1-Day8 were analyzed using the median cut-off for correlations with ORR and PFS. Biomarkers, including CD8+tumor infiltrating lymphocytes (TIL) and interferon-gamma (IFNg) gene expression profile (GEP), were measured in baseline tumor biopsies and analyzed for correlation with ORR and PFS.

Results At median follow-up of 25.7 months (15May2020), ORR by BICR was 53% (20/38 patients). Complete response occurred in 13/38 patients (34%): 23% PD-L1-negative (<1% tumor cell expression); 41% PD-L1-positive (≥1% tumor cell expression). Further deepening of response was observed, with 17/38 patients (45%) achieving 100% reduction in target lesions and a 79% median reduction from baseline in tumor size (previously 62%).1 Median time to response and time to complete response was 2.0 and 7.9 months, respectively. Median PFS and OS were not reached. 2-year OS rate was 77% (95% CI: 60–87; ITT). Safety was consistent with previous reports.1 IFNg GEP and CD8+ TIL in baseline tumor biopsies were significantly associated with ORR and PFS. Analysis of Cycle1-Day8 blood samples demonstrated significant increases in CD4+PSI, CD8+PSI, and eosinophils from baseline. Increased CD8+PSI was significantly associated with higher ORR and PFS; increased eosinophils were significantly associated with higher ORR.

Conclusions BEMPEG plus NIVO was well tolerated in first-line metMEL, with durable and further deepening of responses, regardless of baseline PD-L1 status. At 25.7 months‘ follow-up, mPFS and mOS were not reached. Early on-treatment (Day8) increases in CD8+PSI and eosinophils in blood were identified as non-invasive biomarkers of response that are detectable well before clinical measures of response. A phase 3 trial evaluating BEMPEG plus NIVO in first-line metMEL is enrolling(NCT03635983).

Trial Registration NCT02983045

Ethics Approval The study was approved by the institutional review board of each participating site.


  1. Diab A, Puzanov I, Maio M, et al. Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study. Oral presentation at SITC; November 6–10, 2019; National Harbor, MD, USA. Abstract #O35.

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