RT Journal Article
SR Electronic
T1 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
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000829
DO 10.1136/jitc-2020-000829
VO 8
IS 1
A1 Dmitriy Zamarin
A1 Sven Walderich
A1 Aliya Holland
A1 Qin Zhou
A1 Alexia E Iasonos
A1 Jean M Torrisi
A1 Taha Merghoub
A1 Lewis F Chesebrough
A1 Autumn S Mcdonnell
A1 Jacqueline M Gallagher
A1 Yanyun Li
A1 Travis J Hollmann
A1 Rachel N Grisham
A1 Courtney L Erskine
A1 Mathew S Block
A1 Keith L Knutson
A1 Roisin E O’Cearbhaill
A1 Carol Aghajanian
A1 Jason A Konner
YR 2020
UL http://jitc.bmj.com/content/8/1/e000829.abstract
AB 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.