Post hoc analysis of health-related quality of life in the same patient population is presented in the poster titled “Health-Related Quality of Life (HRQL) in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC) Treated with Cemiplimab: Post Hoc Exploratory Analysis of a Phase 2 Clinical Trial”, also available on the 2020 Fall Clinical Dermatology Conference platform. References 1. Que SKT et al. J Am Acad Dermatol. 2018;78:237–247. 2. Cranmer LD et al. Oncologist. 2010;15:1320–1328. 3. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology: squamous cell skin cancer (Version 2.2019). 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. [Accessed March 20, 2020]. 4. Karia PS et al. J Clin Oncol. 2014;32:327–334. 5. Weinberg AS et al. Dermatol Surg. 2007;33:885–899. 6. Schmults CD et al. JAMA Dermatol. 2013;149:541–547. 7. Cowey C et al. Cancer Med. 2020 [in press]. 8. Burova E et al. Mol Cancer Ther. 2017;16:861–870. 9. Migden MR et al. Lancet Oncol. 2020;21:294–305. 10. Migden MR et al. N Engl J Med. 2018;379:341–351. 11. Rischin D et al. Poster presented at Maui Dermatology Conference, January 25–29, 2020. 12. Eisenhauer EA et al. Eur J Cancer. 2009;45:228–247. Acknowledgments The authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. The study was funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Medical writing support and typesetting was provided by Kate Carolan, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. For any questions or comments, please contact Dr Danny Rischin, Danny.Rischin@petermac.org Disclosures Danny Rischin reports institutional research grant and funding from Regeneron Pharmaceuticals, Inc., Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, and GlaxoSmithKline; uncompensated scientific committee and advisory board from Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, and Bristol-Myers Squibb; travel and accommodation from Merck Sharp & Dohme and GlaxoSmithKline. Nikhil I. Khushalani reports grants from Regeneron Pharmaceuticals, Inc.; grants and advisory board fees from Bristol-Myers Squibb and HUYA Bioscience International; advisory board fees from EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, ARRAY Biopharma, Jounce Therapeutics, and Immunocore; grants from Merck, Novartis, GlaxoSmithKline, Cellgene, and Amgen; honorarium from Sanofi; and common stock ownership of Bellicum Pharmaceuticals, Mazor Robotics, Amarin, and Transenetrix. Chrysalyne D. Schmults reports steering committee member for Castle Biosciences; a steering committee member and consultant for Regeneron Pharmaceuticals, Inc.; a consultant for Sanofi; research funding from Castle Biosciences, Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Merck, and is a chair for the National Comprehensive Cancer Network. Alexander Guminski reports personal fees and non-financial support (advisory board and travel support) from Bristol-Myers Squibb and Sun Pharma; personal fees (advisory board) from Merck KGaA, Eisai, and Pfizer; non-financial (travel) support from Astellas; and clinical trial unit support from PPD Australia. Anne Lynn S. Chang reports consulting and advisory roles at Regeneron Pharmaceuticals, Inc. and Merck; research funding from Regeneron Pharmaceuticals, Inc., Novartis, Galderma, and Merck. Karl D. Lewis reports grants and personal fees from Regeneron Pharmaceuticals, Inc. during the conduct of the study. Annette M. Lim reports uncompensated advisory board from Merck Sharp & Dohme and Bristol-Myers Squibb with travel and accommodation expenses. Leonel Hernandez-Aya reports consulting and advisory roles at Massive Bio; speakers’ bureau roles at Sanofi and Regeneron Pharmaceuticals, Inc.; travel, accommodations, and expenses from Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol-Myers Squibb; research funding from Bristol-Myers Squibb, Regeneron Pharmaceuticals, Inc., Immunocore, Merck Sharp & Dohme, Polynoma, Corvus Pharmaceuticals, Roche, Merck Serono, Amgen, MedImmune, and Takeda. Brett G.M. Hughes reports consulting or advisory roles at Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Pfizer, Roche, Eisai, and Merck; institutional research funding from Amgen. Dirk Schadendorf reports institutional patients’ fees from Regeneron Pharmaceuticals, Inc.; advisory board honorarium fees from Amgen and Leo Pharma; speaker fee from Boehringer Ingelheim; advisory board, speaker honorarium and patients’ fees from Roche, Novartis, Bristol-Myers Squibb, and Merck-EMD; advisory board and speaker honorarium fees from Incyte and Pierre Fabre; advisory board honorarium and patients’ fees from MSD, steering committee honorarium fees from 4SC, advisory board fees from AstraZeneca, Pfizer, and Array; advisory board and patients’ fees from Philiogen. Axel Hauschild reports institutional grants, speaker’s honoraria, and consultancy fees from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche, and Novartis; institutional grants and consultancy fees from Merck Serono, Philogen, and Regeneron Pharmaceuticals, Inc.; consultancy fees from OncoSec. Michael R. Migden reports honoraria and travel expenses from Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly, and Sun Pharma; institutional research funding from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Eli Lilly. Elizabeth Stankevich, Jocelyn Booth, Siyu Li, Zhen Chen, Emmanuel Okoye, Israel Lowy, and Matthew G. Fury are employees and shareholders of Regeneron Pharmaceuticals, Inc. Summary and Conclusion • For patients with advanced CSCC, cemiplimab achieved ORR of 46.1%. • Patients had deepening responses over time as evidenced by increasing complete response rates.9–11 Overall, the complete response rate is now 16.1% and median time to complete response was 11.2 months. • DOR and OS are longer than what has been previously described with other agents.7 • With median DOR not reached after an additional 1 year of follow-up, this analysis indicates an increasing, clinically meaningful DOR with cemiplimab. • The discontinuation rate, regardless of attribution, was low and most TRAEs were Grades 1–2. Synopsis • Cutaneous squamous cell carcinoma (CSCC) is the second most common cancer in the US and its incidence is increasing.1 • Most cases of CSCC are cured by complete surgical excision.2,3 However, a small but substantial number of patients present with either metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) not amenable to curative surgery or curative radiotherapy (collectively referred to as “advanced CSCC”), both of which have poor prognoses.4–6 • Historical data shows median overall survival (OS) of approximately 15 months with conventional chemotherapy or epidermal growth factor receptor inhibitors.7 • Cemiplimab is a high-affinity, highly potent human immunoglobulin G4 monoclonal antibody to the programmed cell death (PD)-1 receptor.8 • Cemiplimab monotherapy achieved clinically meaningful activity in patients with advanced CSCC and has a safety profile consistent with other anti–PD-1 agents.9–11 • Based on initial data (median follow-up of 9.4 months in the pivotal study, NCT02760498), cemiplimab (cemiplimab-rwlc in the US) was approved for the treatment of patients with advanced CSCC. Group 1 – Adult patients with metastatic (nodal and/or distant) CSCC Cemiplimab 3 mg/kg Q2W IV, for up to 96 weeks Cemiplimab 350 mg Q3W IV, for up to 54 weeks Tumor response assessment by ICR (RECIST 1.1 for scans; modified WHO criteria for photos) Tumor imaging every 8 weeks for the assessment of clinical activity Tumor imaging every 9 weeks for the assessment of clinical activity Group 3 – Adult patients with metastatic (nodal and/or distant) CSCC Group 2 – laCSCC Key inclusion criteria • ECOG performance status of 0 or 1 • Adequate organ function • Groups 1 and 3: At least one lesion measurable by RECIST 1.1 • Group 2 At least one lesion measurable by digital medical photography CSCC lesion that is not amenable to curative surgery or curative radiation therapy per investigators’ assessment Tumor biopsies at baseline and on day 29, for exploratory biomarker analysis, unless considered to have unacceptable safety risks by the investigator Key exclusion criteria • Ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression • Prior treatments with anti–PD-1 or anti–PD-L1 therapy • History of solid organ transplant, concurrent malignancies (unless indolent or not considered life-threatening; for example, basal cell carcinoma), or hematologic malignancies Figure 1. Study design ECOG, Eastern Cooperative Oncology Group; IV, intravenously; PD-L1, PD-ligand 1. Phase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer Follow-Up Danny Rischin,1 Nikhil I. Khushalani,2 Chrysalyne D. Schmults,3 Alexander Guminski,4 Anne Lynn S. Chang,5 Karl D. Lewis,6 Annette M. Lim,1 Leonel Hernandez-Aya,7 Brett G.M. Hughes,8 Dirk Schadendorf,9 Axel Hauschild,10 Elizabeth Stankevich,11 Jocelyn Booth,11 Suk-Young Yoo,11 Zhen Chen,12 Emmanuel Okoye,13 Israel Lowy,12 Matthew G. Fury,12 Michael R. Migden14 1Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; 2Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA; 3Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 4Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia; 5Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA; 6University of Colorado Denver, School of Medicine, Aurora, CO, USA; 7Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 8Royal Brisbane & Women’s Hospital and University of Queensland, Brisbane, Australia; 9University Hospital Essen, Essen and German Cancer Consortium, Essen, Germany; 10Schleswig-Holstein University Hospital, Kiel, Germany; 11Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA; 12Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 13Regeneron Pharmaceuticals, Inc., London, UK; 14Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA Results Patients • A total of 193 patients were enrolled (Group 1, n=59; Group 2, n=78; Group 3, n=56) (Table 1). Table 1. Baseline demographics Advanced CSCC (n=193) Median age, years (range) 72.0 (38–96) Male, n (%) 161 (83.4) ECOG performance status, n (%) 0 86 (44.6) 1 107 (55.4) Primary CSCC site: head and neck, n (%) 131 (67.9) mCSCC, n (%) 115 (59.6) laCSCC, n (%) 78 (40.4) Patients with cemiplimab as first-line therapy, n (%) 128 (66.3) Patients with prior systemic therapy, n (%)† 65 (33.7) Median duration of exposure to cemiplimab, weeks (range) 51.1 (2.0–109.3) Median number of doses of cemiplimab administered (range) 18.0 (1–48) †Settings for prior lines of therapy included metastatic disease, adjuvant, chemotherapy with concurrent radiation, or other and the most common types of prior systemic therapy were platinum compounds (n=46/65 [70.8%]) and monoclonal antibodies (n=18/65 [27.7%]). Table 2. Duration of follow-up and tumor response to cemiplimab per ICR Group 1 (mCSCC) 3 mg/kg Q2W (n=59) Group 2 (laCSCC) 3 mg/kg Q2W (n=78) Group 3 (mCSCC) 350 mg Q3W (n=56) Total (n=193) Median duration of follow-up, months (range) 18.5 (1.1–36.1) 15.5 (0.8–35.6) 17.3 (0.6–26.3) 15.7 (0.6–36.1) ORR, % (95% CI) 50.8 (37.5–64.1) 44.9 (33.6–56.6) 42.9 (29.7–56.8) 46.1 (38.9–53.4) Complete response, n (%) 12 (20.3) 10 (12.8) 9 (16.1) 31 (16.1) Partial response, n (%) 18 (30.5) 25 (32.1) 15 (26.8) 58 (30.1) Stable disease, n (%) 9 (15.3) 27 (34.6) 10 (17.9) 46 (23.8) Non-complete response/non-progressive disease, n (%) 3 (5.1) 0 2 (3.6) 5 (2.6) Progressive disease, n (%) 10 (16.9) 10 (12.8) 14 (25.0) 34 (17.6) Not evaluable, n (%) 7 (11.9) 6 (7.7) 6 (10.7) 19 (9.8) Disease control rate, % (95% CI) 71.2 (57.9–82.2) 79.5 (68.8–87.8) 64.3 (50.4–76.6) 72.5 (65.7–78.7) Durable disease control rate,† % (95% CI) 61.0 (47.4–73.5) 62.8 (51.1–73.5) 57.1 (43.2–70.3) 60.6 (53.3–67.6) Median observed time to response, months (IQR)‡ 1.9 (1.8–2.0) 2.1 (1.9–3.8) 2.1 (2.1–4.2) 2.1 (1.9–3.7) Median observed time to complete response, months (IQR) 11.1 (7.5–18.4) 10.5 (7.4–12.9) 12.4 (8.2–16.6) 11.2 (7.4–14.8) Median DOR, months (95% CI)‡ NR (20.7–NE) NR (18.4–NE) NR (NE–NE) NR (28.8–NE) Kaplan–Meier 12-month estimate of patients with ongoing response, % (95% CI) 89.5 (70.9–96.5) 83.2 (64.1–92.7) 91.7 (70.6–97.8) 87.8 (78.5–93.3) Kaplan–Meier 24-month estimate of patients with ongoing response, % (95% CI) 68.8 (46.9–83.2) 62.5 (38.4–79.4) NE (NE, NE) 69.4 (55.6–79.6) †Defined as the proportion of patients without progressive disease for at least 105 days. ‡Based on number of patients with confirmed complete or partial response. ORR per INV was 54.4% (95% CI: 47.1–61.6) for all patients; 50.8% (95% CI: 37.5–64.1) for Group 1, 56.4% (95% CI: 44.7–67.6) for Group 2, and 55.4% (95% CI: 41.5–68.7) for Group 3. ORR per INV was 57.8% (95% CI: 48.8–66.5) among treatment-naïve patients and 47.7% (95% CI: 35.1–60.5) among previously treated patients. CI, confidence interval; NE, not evaluable; NR, not reached. Table 3. TEAEs regardless of attribution Advanced CSCC (n=193) n (%) Any grade Grade ≥3 Any 192 (99.5) 94 (48.7) Led to discontinuation 19 (9.8) 14 (7.3) Most common† Fatigue 67 (34.7) 5 (2.6) Diarrhea 53 (27.5) 2 (1.0) Nausea 46 (23.8) 0 Pruritus 41 (21.2) 0 Rash 32 (16.6) 1 (0.5) Cough 32 (16.6) 0 Arthralgia 28 (14.5) 1 (0.5) Constipation 26 (13.5) 1 (0.5) Vomiting 24 (12.4) 1 (0.5) Actinic keratosis 23 (11.9) 0 Maculopapular rash 23 (11.9) 1 (0.5) Anemia 22 (11.4) 8 (4.1) Hypothyroidism 22 (11.4) 0 Headache 21 (10.9) 0 Upper respiratory tract infection 20 (10.4) 0 †TEAEs reported in ≥10% of patients, ordered by frequency of any grade. • ORR per ICR was 46.1% (95% CI: 38.9–53.4) among all patients; 50.8% (95% CI: 37.5–64.1) for Group 1, 44.9% (95% CI: 33.6–56.6) for Group 2, and 42.9% (95% CI: 29.7–56.8) for Group 3 (Table 2). • Per ICR, ORR was 48.4% and 41.5% among those who had not received prior anticancer systemic therapy (n=128) and those who had received prior anticancer systemic therapy (n=65), respectively. • Overall, the observed time to response was 2 months for 41 (46.1%) patients, 2–4 months for 29 (32.6%) patients, 4–6 months for eight (9.0%) patients, and >6 months for 11 (12.4%) patients. • Median DOR has not been reached (observed DOR range: 1.9–34.3 months). In responding patients, the estimated proportion of patients with ongoing response at 24 months was 69.4% (95% CI: 55.6–79.6) (Figure 3). Treatment-emergent adverse events • In total, 192 (99.5%) patients experienced at least one TEAE of any grade regardless of attribution (Table 3). • Overall, the most common TEAEs of any grade were fatigue (n=67, 34.7%), diarrhea (n=53, 27.5%), and nausea (n=46, 23.8%). • Grade ≥3 TEAEs regardless of attribution occurred in 94 (48.7%) of patients. The most common Grade ≥3 TEAEs were hypertension (n=9; 4.7%) and anemia and cellulitis (each n=8; 4.1%). • Grade ≥3 treatment-related adverse events (TRAEs) were reported in 33 (17.1%) patients, with the most common being pneumonitis (n=5, 2.6%), autoimmune hepatitis (n=3; 1.6%), anemia, colitis, and diarrhea (all n=2; 1.0%). • No new TEAEs resulting in death were reported compared to previous reports.9–11 Clinical activity • Complete response rates at primary analysis, ~1-year follow-up for Groups 1, 2, and 3, and ~2-year follow-up for Group 1 are shown in Figure 2. • Among 89 responders, median time to complete response was 11.2 months (interquartile range [IQR], 7.4–14.8). • Estimated median PFS was 18.4 months (95% CI: 10.3–24.3) for all patients. The Kaplan–Meier estimated progression-free probability at 24 months was 44.2% (95% CI: 36.1–52.1) (Figure 4A). • Median OS has not been reached. The Kaplan–Meier estimated probability of OS at 24 months was 73.3% (95% CI: 66.1–79.2) (Figure 4B). Figure 3. Kaplan–Meier curves of DOR per ICR 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 P ro b a b ili ty o f n o p ro g re s s io n o r d e a th Month Number of patients at risk 30 30 29 28 23 23 23 23 23 20 18 16 16 16 10 9 6 2 0 0 0Group 1 (n=59) 35 33 32 30 27 25 22 21 17 14 10 8 6 6 5 4 0 0 0 0 0Group 2 (n=78) 24 24 24 23 21 21 20 19 17 11 5 0 0 0 0 0 0 0 0 0 0Group 3 (n=56) Total (n=193) 89 87 85 81 71 69 65 63 57 45 33 24 22 22 15 13 6 2 0 0 0 Group 1 (mCSCC) 3 mg/kg Q2W (n=59) Group 2 (laCSCC) 3 mg/kg Q2W (n=78) Group 3 (mCSCC) 350 mg Q3W (n=56) Total (n=193) Figure 2. Complete response rates per ICR 25 20 15 10 5 0 C o m p le te r e s p o n s e r a te s ( % ) Group 1 (mCSCC) 3 mg/kg Q2W Group 2 (laCSCC)† 3 mg/kg Q2W Group 3 (mCSCC) 350 mg Q3W n=10 12.8 n=3 5.4 n=4 6.8 n=10 16.9 n=12 20.3 n=10 12.8 n=9 16.1 Primary ~1-year follow-up ~2-year follow-up Figure 4. Kaplan–Meier curves for A) PFS per ICR and B) OS Group 1 (mCSCC) 3 mg/kg Q2W (n=59) Group 2 (laCSCC) 3 mg/kg Q2W (n=78) Group 3 (mCSCC) 350 mg Q3W (n=56) Total (n=193) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 P ro b a b ili ty o f O S MonthNumber of patients at risk 59 56 52 49 47 46 41 39 39 38 38 37 35 33 24 16 11 4 1 0Group 1 (n=59) 47 78 76 73 67 65 64 62 59 54 44 41 33 25 22 15 12 8 3 1 0Group 2 (n=78) 65 56 52 49 46 45 38 38 38 37 29 20 9 2 0 0 0 0 0 0 0Group 3 (n=56) 44 Total (n=193) 193 184 174 162 157 156 148 141 136 130 111 99 79 62 55 39 28 19 7 2 0 B Group 1 (mCSCC) 3 mg/kg Q2W (n=59) Group 2 (laCSCC) 3 mg/kg Q2W (n=78) Group 3 (mCSCC) 350 mg Q3W (n=56) Total (n=193) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 P ro b a b ili ty o f P F S Month Number of patients at risk 59 42 38 36 32 27 27 27 27 27 24 24 21 20 20 12 9 6 1 0 0Group 1 (n=59) 78 61 48 43 39 37 33 29 26 20 17 16 12 10 7 5 5 2 0 0 0Group 2 (n=78) 56 48 33 31 31 28 26 26 24 24 17 10 1 1 0 0 0 0 0 0 0Group 3 (n=56) 193 151 119 110 102 92 86 82 77 71 58 50 34 31 27 17 14 8 1 0 0Total (n=193) A †Among 23 laCSCC patients who were included in the pre-specified Group 2 interim analysis, there were no complete responses. Presented at the 2020 Fall Clinical Dermatology Conference, October 29–November 1, Virtual Scientific Meeting (encore of ASCO 2020 poster presentation). Objectives • The primary objective of the Phase 2 study was to evaluate the objective response rate (ORR) by independent central review (ICR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) (for scans)12 and modified World Health Organization (WHO) criteria (for photos). • Key secondary objectives included ORR per investigator review (INV), duration of response (DOR) by ICR and INV, progression-free survival (PFS) by ICR and INV, OS, complete response rate by ICR, safety and tolerability, and assessment of health-related quality of life. Durable disease control rate, defined as the proportion of patients with response or stable disease for at least 105 days, was also examined. • Here, we present up to 3-year follow-up (median duration of follow-up for all patients: 15.7 months) from the largest and most mature prospective data set in advanced CSCC. Methods • EMPOWER-CSCC-1 is an open-label, non-randomized, multicenter, international Phase 2 study of patients with advanced CSCC. • Patients received cemiplimab 3 mg/kg every 2 weeks (Q2W) (Group 1; mCSCC; Group 2, laCSCC) or cemiplimab 350 mg every 3 weeks (Q3W) (Group 3, mCSCC) (Figure 1). • The severity of treatment-emergent adverse events (TEAEs) was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). • The data cut-off was October 11, 2019.