TY - JOUR
T1 - Pilot phase II trial of neoadjuvant immunotherapy in locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck
AU - Ferrarotto, Renata
AU - Amit, Moran
AU - Nagarajan, Priyadharsini
AU - Rubin, M. Laura
AU - Yuan, Ying
AU - Bell, Diana
AU - El-Naggar, Adel K.
AU - Johnson, Jason M.
AU - Morrison, William H.
AU - Rosenthal, David I.
AU - Glisson, Bonnie S.
AU - Johnson, Faye M.
AU - Lu, Charles
AU - Mott, Frank E.
AU - Esmaeli, Bita
AU - Diaz, Eduardo M.
AU - Gidley, Paul W.
AU - Goepfert, Ryan P.
AU - Lewis, Carol M.
AU - Weber, Randal S.
AU - Wargo, Jennifer A.
AU - Basu, Sreyashi
AU - Duan, Fei
AU - Yadav, Shalini S.
AU - Sharma, Padmanee
AU - Allison, James P.
AU - Myers, Jeffrey N.
AU - Gross, Neil D.
N1 - Funding Information:
support from Affini-T; other support from Apricity; personal fees and other support from BioAtla; other support from BioNTech; personal fees and other support from Candel Therapeutics; other support from Catalio; personal fees and other support from Codiak Biosciences; other support from Constellation; personal fees and other support from Dragonfly, Earli, Enable Medicine, Glympse, Hummingbird, Imaginab, and Infinity Pharma; personal fees from Jounce Therapeutics; other support from JSL Health; personal fees and other support from Lava Therapeutics, Lytix, Marker, Oncolytics, PBM Capital, Phenomic AI, Polaris Pharma; other support from Sporos and Time Bioventures; and personal fees and other support from Trained Therapeutix and Venn Biosciences outside the submitted work. N.D. Gross reports grants and nonfinancial support from American Academy of Otolaryngolgoy/Head and Neck Surgery Foundation, grants and personal fees from Regeneron, and personal fees from Sanofi-Genzyme during the conduct of the study, as well as personal fees from PDS Biotechnology, Shattuck Labs, and Intuitive Surgical outside the submitted work. No disclosures were reported by the other authors.
Funding Information:
This work is supported by Regeneron, the American Head and Neck Society/ American Academy of Otolaryngology Head and Neck Surgery Foundation Surgeon Scientist Combined award, and by the National Cancer Institute award P30CA016672. We thank the patients and their families for participating in this study and Stephanie P. Deming from the Research Medical Library for editing services.
Funding Information:
R. Ferrarotto reports other support from Regeneron during the conduct of the study, as well as personal fees from Regeneron-Sanofi, Ayala Pharmaceuticals, Klus Pharma, Bicara Therapeutics, Medscape, Carevive Systems, Prelude Therapeutics, and Intellisphere and grants from AstraZeneca, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, and EMD Serono outside the submitted work. Y. Yuan reports personal fees from AbbVie, Amgen, BeyondSpring Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, MicuRx Pharmaceuticals, Servier Pharmaceuticals, Starpax Pharmaceuticals, and Vertex Pharmaceuticals outside the submitted work. W.H. Morrison reports grants from Regeneron during the conduct of the study, as well as personal fees from Regeneron and Sanofi Genzyme outside the submitted work and common stock ownership in Merck. D.I. Rosenthal reports personal fees from Merck outside the submitted work. B.S. Glisson reports grants from Regeneron during the conduct of the study, as well as grants from Pfizer, ISA Pharmaceuticals, and CUE BIO outside the submitted work. F.M. Johnson reports grants from Takeda outside the submitted work. P.W. Gidley reports grants from Regeneron during the conduct of the study, as well as other support from Amgen, Eli Lily, Merck, Pfizer, Novartis, and Roche outside the submitted work. C.M. Lewis reports grants from Regeneron during the conduct of the study. J.A. Wargo reports personal fees from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Bristol-Myers Squibb, Roche/ Genentech, AstraZeneca, GlaxoSmithKline, Merck, Ella Therapeutics, and Micro-noma and grants from Novartis outside the submitted work, as well as a patent for (PCT/US17/53.717) issued to MD Anderson and a patent for UTSC.P1412US.P1 pending to MD Anderson. P. Sharma reports personal fees and other support from Achelois; other support from Adaptive Biotechnologies; personal fees and other
Publisher Copyright:
© 2021 American Association for Cancer Research
PY - 2021/8/15
Y1 - 2021/8/15
N2 - Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence. Patients and Methods: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response. Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR (n = 11) or MPR (n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR. Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.
AB - Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence. Patients and Methods: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response. Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR (n = 11) or MPR (n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR. Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.
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U2 - 10.1158/1078-0432.CCR-21-0585
DO - 10.1158/1078-0432.CCR-21-0585
M3 - Article
C2 - 34187851
AN - SCOPUS:85113786457
SN - 1078-0432
VL - 27
SP - 4557
EP - 4565
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -