Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial

Dmitriy Zamarin, Sven Walderich, Aliya Holland, Qin Zhou, Alexia E. Iasonos, Jean M. Torrisi, Taha Merghoub, Lewis F. Chesebrough, Autumn S. Mcdonnell, Jacqueline M. Gallagher, Yanyun Li, Travis J. Hollmann, Rachel N. Grisham, Courtney L. Erskine, Mathew S. Block, Keith L. Knutson, Roisin E. O'Cearbhaill, Carol Aghajanian, Jason A. Konner

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC. METHODS: Following Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses. RESULTS: Treatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5-∞), with evidence of benefit from postimmunotherapy regimens. CONCLUSIONS: Combination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment.

Original languageEnglish (US)
JournalJournal for ImmunoTherapy of Cancer
Volume8
Issue number1
DOIs
StatePublished - Jun 1 2020

Keywords

  • antigens, neoplasm
  • clinical trials, phase II as topic
  • immunogenicity, vaccine
  • programmed cell death 1 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial'. Together they form a unique fingerprint.

Cite this