A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours

Amit Maity, Rosemarie Mick, Alexander C. Huang, Sangeeth M. George, Michael D. Farwell, John N. Lukens, Abigail T. Berman, Tara C. Mitchell, Josh Bauml, Lynn M. Schuchter, Mark O’Hara, Lilie L. Lin, Angela Demichele, John P. Christodouleas, Naomi B. Haas, Dana M. Patsch, Stephen M. Hahn, Andy J. Minn, E. John Wherry, Robert H. Vonderheide

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Background: We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. Methods: There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response. Results: Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells. Conclusions: HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy. Clinical Trial Registration: NCT02303990 (www.clinicaltrials.gov).

Original languageEnglish
Pages (from-to)1200-1207
Number of pages8
JournalBritish Journal of Cancer
Volume119
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized/therapeutic use
  • Antineoplastic Agents, Immunological/therapeutic use
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Chemoradiotherapy
  • Disease-Free Survival
  • Female
  • Humans
  • Lung Neoplasms/drug therapy
  • Male
  • Melanoma/drug therapy
  • Middle Aged
  • Neoplasm Metastasis/drug therapy
  • Radiation Dose Hypofractionation
  • Skin Neoplasms/drug therapy

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