1136O - Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Immunotherapy of cancer
Topics Cancer in Adolescents
Anal Cancer
Cancer Immunology and Immunotherapy
Presenter Bonnie Glisson
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors B. Glisson1, E. Massarelli2, W.N. William3, F.M. Johnson1, M.S. Kies1, R. Ferrarotto1, M. Guo4, S.A. Peng5, J..J. Lee5, H. Tran1, Y.U. Kim6, C. Haymaker6, C. Bernatchez6, M. Curran7, B. Sanchez Espiridion8, J. Rodriguez Canales8, I.I. Wistuba8, S. van der Burg9, J. Wang10, C. Melief11
  • 1Thoracic/head And Neck Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2Medical Oncology And Therapeutics Research, City of Hope, 91010 - Duarte/US
  • 3Thoracic/head And Neck Medical Oncology, MD Anderson Cancer Center, 770303 - Houston/US
  • 4Pathology Administration, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 5Biostatistics, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 6Melanoma Medical Oncology - Research, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 7Immunology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 8Translational Molecular Pathology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 9Clinical Oncology, Leiden University Medical Center, Leiden/NL
  • 10Bioinformatics & Comp Biology, MD Anderson Cancer Center, 77030 - Houston/US
  • 11Immunohematology, Leiden University Medical Center (LUMC), 2300 RC - Leiden/NL

Abstract

Background

Vaccines directed against Human Papilloma Virus (HPV) do not generally mediate regression of invasive cancer. To test the hypothesis that the efficacy of vaccine-induced T cells may be amplified through treatment with immune checkpoint antibodies, we conducted a phase II trial of ISA 101, a synthetic long-peptide HPV-16 vaccine, and nivolumab in pts with incurable HPV-16+ cancer.

Methods

Tumors were HPV-genotype 16 by Cervista HPV16/18. Patients were ECOG PS 0-1 with up to one prior regimen for recurrence. ISA101 100 mcgs/peptide was given Days 1, 22, 50. Nivolumab 3 mg/kg was given iv every 2 wks beginning day 8 for up to one year. Imaging was obtained baseline, 11 wks and every 6 wks thereafter. The primary objective was assessment of overall response rate (ORR) targeting 30%. Secondary objectives: tolerability, PFS, OS. A Simon two stage design required response in 2/15 first stage and 5/25 in second stage.

Results

The trial accrued 24 patients; 22 with oropharynx cancer (OPC) and 1 pt each with anal and cervical cancer. 18 pts (75%) had progression within 6 mos of prior platin and 1 was platin-naïve. 12 pts (50%) had prior cetuximab. Treatment was frontline for recurrence in 10/24 and second line in 14/24. ORR is 33% (8/24): 1 CR, 7 PR (1 unconfirmed), 3(13%) SD, 13 (54%) PD. ORR in OPC pts is 36% (8/22). 6/8 pts with PR progressed within 6 mos of prior platin. Median duration of response 30.1+ wks (6- 49+ wks); 5/8 pts with PR remain in response. Median PFS is 2.7 mos [95% CI 2.3-8.0 mos] and median OS is not reached with median follow up time among censored pts 8.6 mos. PFS rate at 6 mos: 33%, [16-52%] OS rate at 6 mos 74%, [51-87%] . Toxicity: grade 3 transaminase and grade 4 lipase elevation in 1 pt each, grade 1-2 toxicity: fever (5 pts), injection site reaction (6 pts), transaminase elevation, fatigue, nausea (3 pts each).

Conclusions

The primary endpoint was met and ORR of 36% in OPC pts compares favorably to 16% for nivolumab monotherapy in p16+ OPC pts in Checkmate 141 (Ferris RL et al N Engl J Med 2016; 375:1856). These data suggest that the efficacy of vaccine-induced T cells can be augmented by anti-PD-1 therapy, mitigating the influence of an immunosuppressive microenvironment. Our findings merit confirmation in a larger randomized trial. Correlation of efficacy outcomes with immunoprofiling of tumors will be presented.

Clinical trial identification

NCT02426892

Legal entity responsible for the study

U T M D Anderson Cancer Center

Funding

U T M D Anderson Cancer Center

Disclosure

S. van der Burg, C. Melief: Employed by ISA Pharmaceuticals Inc. All other authors have declared no conflicts of interest.