Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody

Evan J. Lipson, William H. Sharfman, Charles G. Drake, Ira Wollner, Janis M. Taube, Robert A. Anders, Haiying Xu, Sheng Yao, Alice Pons, Lieping Chen, Drew M. Pardoll, Julie R. Brahmer, Suzanne L. Topalian

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term followup on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective. Experimental Design: Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy. Results: A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti- PD-1 therapy. Conclusion: These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalClinical Cancer Research
Volume19
Issue number2
DOIs
StatePublished - Jan 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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