Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders.

"Competing interests: BMH has received honorarium from TD Cowen for consulting. JMC has received funding to her institution for research from Lilly and Sanofi. She has served as a consultant or on advisory boards for Novartis/AAA, Ipsen, Curium, and TerSera. She has received royalties from UpToDate. She owns stock in Merck. JAM received an honorarium for being on the advisory board of Merck. NJM received funding to her institution for research from Bristol Myers Squibb. MBY received research funding from Janssen Pharmaceuticals and fees for peer review services from UpToDate. BR has institutional patents filed on methods for clinical interpretation. EMVA has served in an advisory/consulting role for Tango Therapeutics, Genome Medical, Genomic Life, Enara Bio, Manifold Bio, Monte Rosa, Novartis Institute for Biomedical Research, Riva Therapeutics, and Serinus Bio. He receives research support from Novartis, BMS, and Sanofi. He has investment equity in Tango Therapeutics, Genome Medical, Genomic Life, Syapse, Enara Bio, Manifold Bio, Microsoft, Monte Rosa, Riva Therapeutics, Serinus Bio. He holds institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation; intermittent legal consulting on patents for Foaley & Hoag. AP has equity in C2i Genomics XGenomes and Parithera and in the last 36 months, has served as an advisor/consultant for Eli Lilly, Pfizer, Inivata, Biofidelity, Checkmate Pharmaceuticals, FMI, Guardant, Abbvie, Bayer, Delcath, Taiho, CVS, Value Analytics Lab, Seagen, Saga, AZ, Scare, Illumina and Science For America. She receives fees from Up to Date. She has received travel fees from Karkinos Healthcare. She has been on the DSMC for a Roche study and on Steering Committee for Exilixis. She has received research funding to the Institution from PureTech, PMV Pharmaceuticals, Plexxicon, Takeda, BMS, Mirati, Novartis, Erasca, Genentech, and Daiichi Sankyo. KN has received research funding to her institution from Pharmavite, Evergrande Group, Janssen, and Revolution Medicines. She has consulted or served on advisory boards for Bayer, Pfizer, and GSK. SK, CDVF, and CK are employed by Naveris, Inc. and may hold equity or stock options in Naveris, Inc. ALC received research funding unrelated to this project from Novocure, Astrazeneca, Amgen, Nucana, Gilead, Tanabe, Seagen. DAR has served in a consulting or advisory role for Boston Scientific, Instylla, Taiho, and AxialTx. SKD received research funding unrelated to this project from Eli Lilly and Company, Novartis Pharmaceuticals, Genocea, and Bristol-Myers Squibb and is a founder, science advisory board member (SAB) and equity holder in Kojin. JMC receives research funding to his institution from Merus, Roche, Servier, and Bristol Myers Squibb. He receives research support from Merck, AstraZeneca, Esperas Pharma, Bayer, Tesaro, Arcus Biosciences, and Apexigen; he has also received honoraria for being on the advisory boards of Incyte and Blueprint Medicines. The remaining authors report no conflicts of interest."

"Funding: This trial was funded by Merck. This study was also supported by the Donna V. Toelke Fund for Cancer Research, the Margaret Anthony Family Fund, and the Maggie and Don Swift Fund. The work of JMC is supported by Stand Up to Cancer, the Lustgarten Foundation, Hale Family Center for Pancreatic Cancer Research and Breakthrough Cancer. The work was also supported by a grant from the National Institutes of Health (P50CA127003). MTH was funded by a Baruj Benacerraf Fellowship. SKD was funded by NIH 1R01AI158488-01, U01 CA274276-01 and the Ludwig Center at Harvard."

"This was a multicenter, open label, single arm phase II clinical trial of pembrolizumab in advanced anal cancer (ClinicalTrials.gov identifier: NCT02919969). Eligible patients had an incurable locally advanced or metastatic anal squamous cell carcinoma. Patients who received previous treatment or who had newly diagnosed incurable disease were eligible for protocol therapy. Additional eligibility requirements included age 18 years, measurable disease according to Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST V.1.1) criteria, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Key exclusion criteria included active autoimmune disease requiring systemic immunosuppressive treatment, known active central nervous system metastases, and prior PD-1/PD-L1-directed immunotherapy. Patients with medically controlled hepatitis B virus or hepatitis C virus were eligible. HIV-positive patients were eligible if their CD4+ count ≥300 cells/µL, if they had undetectable viral load, and were receiving highly active antiretroviral therapy. The study protocol and all amendments were approved by the participating sites’ institutional review board (IRB) (). All patients provided written informed consent. This investigator-initiated trial was funded by Merck, who approved the final manuscript."