5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC

Summary

This study is being done because both 5-azacytidine and nivolumab can influence the immune system's response to HPV-associated head and neck cancer, and we wish to evaluate whether taking 5-azacytidine will make HPV-associated head and neck cancer more sensitive to treatment with nivolumab. 5-Azacytidine (5-AZA) is a chemotherapy, and nivolumab is an immunotherapy. Both drugs are approved for use in the US by the Food and Drug Administration (FDA) for use in the treatment of different types of cancer, and nivolumab is approved for use in head and neck cancer that has previously been treated with chemotherapy. Because they are not approved to be used together in HPV-associated head and neck cancer, these drugs are considered experimental in this study. For this study, the drugs will be used either together or separately.

Timeline

Start

2023-03-23

Primary completion

2028-06-30

Completion

2028-11-30

Publications

• Results Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
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• Results Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8. Epub 2018 Nov 30.
• Results Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
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• Results Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LS, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou L, Jo VY, Stachler MD, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, Adkins DR. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Clin Cancer Res. 2020 Oct 1;26(19):5140-5152. doi: 10.1158/1078-0432.CCR-20-1695. Epub 2020 Jul 14.
• Results Schoenfeld JD, Hanna GJ, Jo VY, Rawal B, Chen YH, Catalano PS, Lako A, Ciantra Z, Weirather JL, Criscitiello S, Luoma A, Chau N, Lorch J, Kass JI, Annino D, Goguen L, Desai A, Ross B, Shah HJ, Jacene HA, Margalit DN, Tishler RB, Wucherpfennig KW, Rodig SJ, Uppaluri R, Haddad RI. Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1563-1570. doi: 10.1001/jamaoncol.2020.2955.
• Results Cannataro VL, Gaffney SG, Sasaki T, Issaeva N, Grewal NKS, Grandis JR, Yarbrough WG, Burtness B, Anderson KS, Townsend JP. APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma. Oncogene. 2019 May;38(18):3475-3487. doi: 10.1038/s41388-018-0657-6. Epub 2019 Jan 15.
• Results Hajek M, Sewell A, Kaech S, Burtness B, Yarbrough WG, Issaeva N. TRAF3/CYLD mutations identify a distinct subset of human papillomavirus-associated head and neck squamous cell carcinoma. Cancer. 2017 May 15;123(10):1778-1790. doi: 10.1002/cncr.30570. Epub 2017 Mar 13.
• Results Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015 Jan 29;517(7536):576-82. doi: 10.1038/nature14129.
• Results Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Clin Cancer Res. 2017 Dec 1;23(23):7276-7287. doi: 10.1158/1078-0432.CCR-17-1438. Epub 2017 Sep 15.
• Results Faden DL, Ding F, Lin Y, Zhai S, Kuo F, Chan TA, Morris LG, Ferris RL. APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma. Oral Oncol. 2019 Sep;96:140-147. doi: 10.1016/j.oraloncology.2019.07.020. Epub 2019 Jul 30.
• Results Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, Sher X, Liu XQ, Lu H, Nebozhyn M, Zhang C, Lunceford JK, Joe A, Cheng J, Webber AL, Ibrahim N, Plimack ER, Ott PA, Seiwert TY, Ribas A, McClanahan TK, Tomassini JE, Loboda A, Kaufman D. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018 Oct 12;362(6411):eaar3593. doi: 10.1126/science.aar3593.
• Results Glimelius B, Lahn M. Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology. Ann Oncol. 2011 Aug;22(8):1717-25. doi: 10.1093/annonc/mdq622. Epub 2011 Jan 13.
• Results Zandberg DP, Ferris RL. Window Studies in Squamous Cell Carcinoma of the Head and Neck: Values and Limits. Curr Treat Options Oncol. 2018 Oct 27;19(12):68. doi: 10.1007/s11864-018-0587-0.
• Results Levy BP, Giaccone G, Besse B, Felip E, Garassino MC, Domine Gomez M, Garrido P, Piperdi B, Ponce-Aix S, Menezes D, MacBeth KJ, Risueno A, Slepetis R, Wu X, Fandi A, Paz-Ares L. Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Eur J Cancer. 2019 Feb;108:120-128. doi: 10.1016/j.ejca.2018.11.028. Epub 2019 Jan 14.
• Results Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, Rekhtman N, Anders RA, Cuda JD, Illei PB, Gabrielson E, Askin FB, Niknafs N, Smith KN, Velez MJ, Sauter JL, Isbell JM, Jones DR, Battafarano RJ, Yang SC, Danilova L, Wolchok JD, Topalian SL, Velculescu VE, Pardoll DM, Brahmer JR, Hellmann MD, Chaft JE, Cimino-Mathews A, Taube JM. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol. 2018 Aug 1;29(8):1853-1860. doi: 10.1093/annonc/mdy218.
• Results Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nat Commun. 2018 Aug 10;9(1):3196. doi: 10.1038/s41467-018-05032-8.
• Results Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst. 2015 Feb 3;107(3):dju435. doi: 10.1093/jnci/dju435. Print 2015 Mar.

Drugs

Indications