Phase I/Ib clinical and immunologic assessment of immunotherapeutic vaccine, DPX-Survivac in women with ovarian, Fallopian tube, or peritoneal cancer (OC).

Wilson, Michelle; Villella, Jeannine; Berinstein, Neil L.; Brown, Jennifer G.; Lheureux, Stéphanie; Haley, Anna; Odunsi, Kunle; Karkada, Mohan; Nemunaitis, John; Morse, Michael A.; Pejović, Tanja; Bentley, J.; Weir, Genevieve; MacDonald, Lisa; Sammatur, Leeladhar; Stanford, Marianne M.; Burzykowski, Tomasz; Nigam, Rita; Mansour, Marc; Oza, Amit M.

doi:10.1200/jco.2014.32.15_suppl.5555

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“…22 Several vaccines have been previously explored in OC, primarily focusing on targeting of cancer-germline antigens (eg, NY-ESO-1) and proteins known to be overexpressed in OC (eg, p53, survivin, MUC1). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] The majority of the studies unfortunately failed to yield substantial evidence of clinical response. Recent studies have highlighted that despite the development of vaccine-specific immune responses, the generated tumor-specific T cells are still likely subject to exhaustion and other immunosuppressive mechanisms active within the tumor microenvironment.…”

Section: Association Of Clinical Benefit With Tumor Microenvironment mentioning

confidence: 99%

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

Zamarin

Walderich

Holland

et al. 2020

J Immunother Cancer

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BackgroundImmune 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.MethodsFollowing 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.ResultsTreatment 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.ConclusionsCombination 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.

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Section: Association Of Clinical Benefit With Tumor Microenvironment mentioning

confidence: 99%

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

Zamarin

Walderich

Holland

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

Phase I/Ib clinical and immunologic assessment of immunotherapeutic vaccine, DPX-Survivac in women with ovarian, Fallopian tube, or peritoneal cancer (OC).

Cited by 1 publication

References 0 publications

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

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

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