Presented at Winter Clinical Derm 2023, January 13–18, 2023 (encore of previous presentation at the European Society of Medical Oncology [ESMO] 2022, September 8–13, Rabinowits G et al.). Reused with permission. Background • CSCC is one of the most commonly diagnosed cancers worldwide, but epidemiologic information of the condition is very limited. • Patient survival rates after early diagnosis of CSCC are good, but morbidity and mortality rates in patients with advanced CSCC not amenable to curative surgery or curative radiotherapy remain high, leaving a significant unmet need.1 • Cemiplimab is a high-affinity, highly potent, fully human, immunoglobulin G4 monoclonal antibody to the programmed cell death (PD)-1 receptor, derived using VelocImmune technology.2 • Cemiplimab (cemiplimab-rwlc in the USA) is approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of adult patients with locally advanced or metastatic CSCC who are not candidates for curative surgery or curative radiation; adult patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with (US prescribing information [USPI])3/progressed on (Summary of Product Characteristics [SmPC])4 a hedgehog pathway inhibitor, or for whom a hedgehog pathway inhibitor is not appropriate (USPI)3/intolerant (SmPC),4 and for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer who are not candidates for surgery or definitive chemoradiation and whose tumors have a tumor proportion score of ≥50% and with no EGFR, ALK, or ROS1 aberrations.3,4 • Limited data exist on the clinical characteristics, management, disease progression, and survivorship of patients with advanced CSCC in real-world clinical practice. • Here, we describe the demographics, effectiveness, and safety of an initial cohort of patients with advanced CSCC treated with cemiplimab in real-world clinical practice and enrolled in the CASE study (NCT03836105). CemiplimAb-rwlc Survivorship and Epidemiology (CASE): A prospective study of the safety and efficacy of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) in a real-world setting Guilherme Rabinowits,1 Jade Homsi,2 Soo J Park,3 Nikhil Khushalani,4 Timothy Panella,5 David M Ellison,6 Rhonda W Gentry,7 Suraj S Venna,8 John Strasswimmer,9 Richard Zuniga,10 Sunandana Chandra,11 Emily S Ruiz,12 Michael R Migden,13 Sherrif F Ibrahim,14 Nikita Mehta,15 Timothy Inocencio,16 Xuanyao He,16 Haixin R Zhang,16 Kathryn Gillis,16 Jean-Francois Pouliot16 1Department of Hematology and Oncology, Miami Cancer Institute/Baptist Health South Florida, Miami, FL, USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Division of Hematology and Oncology, University of California San Diego, San Diego, CA, USA; 4Moffitt Cancer Center, Tampa, FL, USA; 5University of Tennessee Medical Center, Knoxville, TN, USA; 6Charleston Oncology, Charleston, SC, USA; 7CARTI Cancer Center, Little Rock, AR, USA; 8Inova Schar Cancer Institute Melanoma Center, Fairfax, VA, USA; 9College of Medicine (Dermatology) and College of Sciences (Biochemistry), Florida Atlantic University, Boca Raton, FL, USA; 10New York Cancer and Blood Specialists, Port Jefferson, NY, USA; 11Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 12Brigham and Women’s Hospital, Boston, MA, USA; 13University of Texas MD Anderson Cancer Center, Houston, TX, USA; 14Rochester Dermatologic Surgery, PC, Victor, NY, USA; 15Sanofi, Cambridge, MA, USA; 16Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Results Baseline demographics and disease characteristics • As of February 9, 2022, 198 patients were enrolled in the CASE study CSCC cohort, 37 (18.7%) of whom were immunocompromised/immunosuppressed (IC/IS). • Of the total enrolled patient population,196 patients (including 36 who were IC/IS) received at least one dose of cemiplimab (full analysis set). • Demographics and safety data presented here are from the full analysis set; response assessment data is shown for patients who enrolled prior to starting cycle 3 of cemiplimab treatment. • Median age was 76.0 years (range: 33.0–98.0), 75.5% of patients were male, and 90.3% were White (Table 1). • IC/IS patients were investigator reported and identified as having one or more of the following diagnoses in medical history: – Inflammatory bowel diseases – Leukemia – Lupus – Lymphoma – Multiple myeloma – Multiple sclerosis – Rheumatoid arthritis – Polycythemia vera – Myeloproliferative disorder – Chronic obstructive pulmonary disease with prednisone – Undergone allogenic bone marrow or solid organ transplantation Conclusions • Observational studies such as CASE enroll a broader, real-world patient population that is not limited by stricter eligibility criteria. • The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of patients with advanced CSCC was generally consistent with that observed in clinical trials (NCT02383212, NCT02760498), considering real-world practice setting and a broader patient population. • In this initial cohort of patients who were identified as IC/IS, the safety, tolerability, and effectiveness of cemiplimab was consistent with the overall patient population. • Further follow-up and future analyses will provide additional outcomes measures and understanding of cemiplimab in the real-world setting (and during the COVID-19 pandemic), in patients with advanced CSCC and the subset of those who are IC/IS. References 1. de Jong E et al. J Eur Acad Derm Venereol. 2021;36(Suppl. 1):6–10. 2. Burova E et al. Mol Cancer Ther. 2017;16:861–870. 3. Regeneron Pharmaceuticals, Inc. LIBTAYO® [cemiplimab-rwlc] injection full US prescribing information. Available from: https://www. accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf [Accessed Jul 9, 2022]. 4. European Medicines Agency. LIBTAYO® EPAR. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/libtayo [Accessed Jul 25, 2022]. Acknowledgments The authors 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 Jenna Lee, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosures Guilherme Rabinowits reports consulting/advisory roles for EMD Serono, Pfizer, Sanofi, Regeneron Pharmaceuticals, Inc., and Merck and Castle; and stock/other ownership interests from Syros Pharmaceuticals and Regeneron Pharmaceuticals, Inc. Figure 1. Study schema CSCC, cutaneous squamous cell carcinoma; DCR, disease control rate; irAE, immune-related adverse event; IRR, infusion-related reaction; ORR, objective response rate; TSAR, treatment-related serious adverse reaction. Patients with advanced CSCC who are not candidates for surgery/radiation and who recently initiated cemiplimab treatment N=250–350 Study endpoints • Effectiveness: ORR and DCR • Safety: irAEs, IRRs, and TSARs Follow-up for 3 years Off study at 3 years Data collected at naturally occurring visits (every ~3 months) Table 1. Baseline demographics and tumor characteristics Characteristic Total (N=196) Age, median (range), years 76.0 (33–98) Male, n (%) 148 (75.5) White, n (%) 177 (90.3) ECOG performance status, n (%) 0 43 (21.9) 1 89 (45.4) 2 18 (9.2) 3 2 (1.0) Missing 44 (22.4) Metastatic CSCC, n (%) 72 (36.7) Locally advanced CSCC, n (%) 124 (63.3) Current skin lesion locations, n (%) Head and neck 136 (69.4) Thorax and abdomen 18 (9.2) Upper and lower extremities 54 (27.6) Not known 9 (4.6) Missing 3 (1.5) Patients with prior radiation therapy, n (%) 84 (42.9) Patients with prior surgery, n (%) 147 (75.0) Patients with prior systemic therapy, n (%) 89 (45.4) Multidisciplinary input, n (%) 85 (43.4) CSCC, cutaneous squamous cell carcinoma; ECOG, Eastern Cooperative Oncology Group. Figure 2. Duration of treatment exposure N u m b e r o f p a ti e n ts (N = 1 9 6 ) Weeks ≥0 ≥3 ≥6 ≥12 ≥18 ≥24 ≥30 ≥36 ≥42 ≥48 196 (100%) 183 (93.4%) 174 (88.8%) 138 (70.4%) 120 (61.2%) 97 (49.5%) 81 (41.3%) 68 (34.7%) 57 (29.1%) 48 (24.5%) 250 200 150 100 50 0 Table 3. Safety data n (%) Total (N=196) IC/IS (n=36) Any treatment-related SAR 9 (4.6) 1 (2.8) Led to discontinuation 5 (2.6) 0 Led to death 1 (0.5) 0 Colitis 2 (1.0) 0 Adrenal insufficiency 1 (0.5) 0 Autoimmune hepatitis 1 (0.5) 0 Encephalitis 1 (0.5) 0 Pneumonia 1 (0.5) 0 Urosepsis 1 (0.5) 0 Hyperglycemia 1 (0.5) 0 Acute kidney injury 1 (0.5) 1 (2.8) Pneumonitis 1 (0.5) 0 Any treatment-related irAE 49 (25.0) 7 (19.4) Any infusion-related reaction 1 (0.5) 0 IC/IS, immunocompromised/immunosuppressed; irAE, immune-related adverse event; SAR, serious adverse reaction. Table 2. Tumor response to cemiplimab Patients who enrolled prior to Cycle 3 (N=174) ORR, % (95% CI) 37.4 (30.2–45.0) Best overall response, n (%) Complete response 17 (9.8) Partial response 48 (27.6) Stable disease 30 (17.2) Progressive disease 13 (7.5) Mixed response 4 (2.3) Unable to evaluate 3 (1.7) Not applicable 7 (4.0) DCR, % (95% CI) 54.6 (46.9–62.1) Most mixed responses were evaluated by physician visual assessment and were not included in the calculation of ORR or DCR. CI, confidence interval; DCR, disease control rate; ORR, objective response rate. Table 4. Treatment discontinuation Total (N=196) Treatment ongoing, n (%) 85 (43.4) Treatment discontinued, n (%) 111 (56.6) Primary reason for treatment discontinuation, n (%)† Adverse event 13 (11.7) Complete response 6 (5.4) Death 4 (3.6) Disease progression 17 (15.3) Lost to follow-up 1 (0.9) Non-compliance 2 (1.8) Other 16 (14.4) Patient initiated CSCC-related drug treatment 3 (2.7) Patient initiated CSCC-related surgery 3 (2.7) Patient withdrawal 19 (17.1) Physician decision 27 (24.3) Primary reason for follow-up discontinuation, n (%)‡ Completed 1 (1.6) Death 29 (46.8) Disease progression 4 (6.5) Lost to follow-up 3 (4.8) Patient withdrawal 18 (29.0) Physician decision 3 (4.8) Other 4 (6.5) †Percentages are calculated from the number of patients who discontinued treatment (n=111). ‡Percentages are calculated from the number of patients who discontinued from follow-up (n=62). CSCC, cutaneous squamous cell carcinoma. Methods • CASE is a prospective, non-interventional, multi-center, real-world, longitudinal study evaluating effectiveness, safety, QoL, and survivorship in patients with advanced CSCC treated with cemiplimab (Figure 1). • The median duration of cemiplimab exposure was 23.3 weeks (interquartile range: 9.1–47.1) (Figure 2). Tumor response • Efficacy was evaluated in patients who were enrolled prior to starting cycle 3 of cemiplimab treatment (n=174). – Twenty-two patients were not included in the analysis, as informed consent and study enrollment were on or after the third dose of cemiplimab. • The ORR as assessed and reported by the investigator for these patients was 37.4% (95% confidence interval [CI]: 30.2–45.0%; Table 2). – Seventeen (9.8%) patients had a complete response, and 48 (27.6%) patients had a partial response. • The ORR for the IC/IS population of patients who were enrolled prior to starting cycle 3 (n=28) was 42.9% (95% CI: 24.5–62.8%). • The DCR per investigator assessment was 54.6% (95% CI: 46.9–62.1%; Table 2). Safety data • Safety was evaluated in all patients included in the study (n=196). • Nine (4.6%) patients experienced a treatment-related serious adverse event (Table 3). • Forty-nine (25.0%) patients experienced a treatment-related irAE, with the most common being hypothyroidism in 15 (7.7%) patients (Table 3). • There was one event of death attributed to a treatment-related serious adverse event of pneumonitis (Table 3). • Thirteen (11.7%) patients discontinued due to an adverse event (Table 4). • In general, cemiplimab was well-tolerated in IC/IS patients: – One (2.8%) patient experienced a treatment-related serious adverse event of acute kidney injury (Table 3). – Seven (19.4%) patients experienced a treatment-related irAE (Table 3), including: – Increased alanine aminotransferase – Increased aspartate aminotransferase – Pruritus – Hypothyroidism – Increased blood creatinine – Decreased lymphocyte count – Maculo-papular rash – Acute kidney injury – Fatigue Limitations • Not all patients were enrolled and followed within the study from the time of treatment, and there is inherent bias associated with observational studies versus a prospective interventional study. Objectives • The objectives of the CASE study are to, in patients with advanced CSCC or BCC in real-world clinical settings who received cemiplimab 350 mg administered intravenously (IV) every 3 weeks (Q3W): – Describe effectiveness based on objective response rate (ORR) and disease control rate (DCR). – Evaluate the safety of cemiplimab based on incidence of treatment-related immune-related adverse events (irAEs), infusion-related reactions, and treatment-related serious adverse reactions. – Investigate long-term effectiveness and quality of life (QoL). • Adult patients (aged ≥18 years) who had recently started or planned to start treatment of CSCC or BCC with commercially available cemiplimab 350 mg IV Q3W per the approved indication and routine standard of care at one of 43 US academic and community centers were eligible to be enrolled. • Patients were excluded if they were receiving cemiplimab for indications other than CSCC or advanced BCC, or if they had any condition that might interfere with participation in the study, restrict compliance with the treatment plan, or prevent completion of QoL assessments. • Tumors were assessed by computed tomography or magnetic resonance imaging, and response assessments were performed according to Response Evaluation Criteria in Solid Tumours version 1.1. • The data cut-off was February 9, 2022. 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