Presented at Winter Clinical Derm 2023, January 13–18, 2023 (encore of previous presentation at the American Association for Cancer Research [AACR] 2022 Annual Meeting, April 8–13, Lewis KD et al.). Reused with permission.

Primary analysis of Phase 2 results for cemiplimab in patients with metastatic  
basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors

Karl D Lewis,1 Ketty Peris,2,3 Aleksandar Sekulic,4 Alexander J Stratigos,5 Lara Dunn,6 Zeynep Eroglu,7 Anne Lynn S Chang,8 Michael R Migden,9 Suk-Young Yoo,10 Kosalai Mohan,10 Ebony Coates,10 Emmanuel Okoye,10 Jean-François Baurain,11  
Oliver Bechter,12 Axel Hauschild,13 Marcus O Butler,14 Leonel Hernandez-Aya,15† Lisa Licitra,16,17 Rogerio I Neves,18‡ Emily S Ruiz,19 Frank Seebach,10 Israel Lowy,10 Priscila Goncalves,10 Matthew G Fury10

1Department of Medicine-Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA; 2Department of Medicine and Translational Surgery, Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy; 3Department of Medical and Surgical Sciences, Dermatology, Fondazione Policlinico Universitario A Gemelli-IRCCS, Rome, Italy; 4Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA; 
5First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, School of Medicine, Andreas Sygros Hospital, Athens, Greece; 6Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 7Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA; 8Dermatology Department, Stanford University School of 

Medicine, Redwood City, CA, USA; 9Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 10Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 11Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium; 12Department of General Medical Oncology, University Hospitals, 
Leuven, Belgium; 13Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany; 14Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; 15Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 16Department of Medical Oncology Head 

and Neck Cancer, Istituto Nazionale dei Tumori, Milan, Italy; 17Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; 18Division of Plastic Surgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; 19Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

†Current affiliation: Department of Internal Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; ‡Current affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Background
• In the US, basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, 

with approximately 2.8 million cases per year, leading to >3000 deaths annually.1,2

• Hedgehog inhibitors (HHIs), such as vismodegib and sonidegib, are approved for the 
treatment of patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who 
are not candidates for surgery or radiation.3,4

• Until recently, there were no approved agents for the treatment of BCC in patients who 
experienced progression of disease on HHI therapy, or who were intolerant to prior  
HHI therapy.

• Cemiplimab, an immunoglobulin G4 monoclonal antibody derived using VelocImmune® 
technology, is a fully human, hinge-stabilized, high-affinity, high-potency blocker of 
programmed cell death-1 (PD-1).5

• In a pivotal Phase 2 study of patients with advanced BCC who discontinued HHI therapy 
due to progressive disease, intolerance, or no better than stable disease after 9 months 
(NCT03132636), cemiplimab became the first systemic therapy to show clinical benefit in 
patients with laBCC after HHI therapy, with estimated duration of response (DOR) 
exceeding 1 year in 85% of responders.6

• Cemiplimab is approved in the US (generic name: cemiplimab-rwlc) for treatment of 
mBCC or laBCC in patients previously treated with an HHI or for whom HHI therapy is not 
appropriate. Cemiplimab-rwlc is approved in the US in certain patients with advanced 
cutaneous squamous cell carcinoma (CSCC).7

• In Europe, Canada, and Brazil, cemiplimab is also approved in certain patients with 
advanced BCC and CSCC.8–11

Objective
• Here, we present primary data analysis of patients in the mBCC cohort from the 

pivotal Phase 2 study of cemiplimab in advanced BCC.

Key takeaways
• Cemiplimab provided clinically meaningful antitumor activity, including durable 

responses, in patients with mBCC who had progressed on or were intolerant to 
HHI therapy.

• The safety profile was generally consistent with that previously described for 
cemiplimab and other PD-1 inhibitors.

Conclusion
• These results complement those previously reported for the laBCC cohort,6 and 

together indicate that cemiplimab is highly active in advanced BCC tumors.

References
1. Puig S et al. Clin Transl Oncol. 2015;17:497–503.
2. Mohan SV et al. Curr Dermatol Rep. 2014;3:40–45.
3. Sun Pharma Global FZE. Available from: https://www.accessdata.fda.gov/

drugsatfda_docs/label/2017/205266s004lbl.pdf. Accessed June 10, 2021.
4. Roche. Available from: https://www.gene.com/download/pdf/erivedge_

prescribing.pdf. Accessed June 10, 2021.
5. Burova E et al. Mol Cancer Ther. 2017;16:861–870.
6. Stratigos AJ et al. Lancet Oncol. 2021;22:848–857.
7. Regeneron Pharmaceuticals, Inc. Available from: https://www.accessdata.fda.gov/

drugsatfda_docs/label/2021/761097s007lbl.pdf. Accessed January 28, 2022.
8. European Medicines Agency. Available from: https://www.ema.europa.eu/en/

medicines/human/EPAR/libtayo. Accessed December 3, 2021.

9. Sanofi-aventis Canada, Inc. Available from: https://pdf.hres.ca/dpd_
pm/00063482.PDF. Accessed February 23, 2022.

10. Health Canada. Available from: https://www.canada.ca/en/health-canada/
services/drugs-health-products/drug-products/notice-compliance/conditions/
libtayo-notice-compliance-conditions-218718.html. Accessed January 28, 
2022.

11. Brazilian Health Authority - ANVISA. Available from: https://www.gov.br/anvisa/
pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/libtayo-
cemiplimabe-nova-indicacao. Accessed January 28, 2022.

12. Eisenhauer EA et al. Eur J Cancer. 2009;45:228–247.

Acknowledgments
The authors thank the patients, their families, investigators, and all investigational site members involved in this study. This study was 
funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Medical writing support was provided by Daniel M Himmel, PhD, of Prime, 
Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. 

Disclosure
Karl D Lewis reports grants and personal fees from Regeneron Pharmaceuticals, Inc., during the conduct of the study; consulting or 
advisory roles from Array BioPharma, Merck, Roche, Regeneron Pharmaceuticals, Inc., Sanofi, and Iovance Biotherapeutics; travel, 
accommodations, and expenses from Merck, Roche/Genentech, Regeneron Pharmaceuticals, Inc., Neon Therapeutics, and Alkermes; 
honoraria from Array BioPharma and Iovance Biotherapeutics; institutional research funding from Roche/Genentech, Merck, Array 
BioPharma, Incyte, Nektar, Iovance Biotherapeutics, Bristol-Myers Squibb, Kartos Therapeutics, OncoSec, Regeneron Pharmaceuticals, 
Inc., Alkermes, Neon Therapeutics, Ultimovacs, Senhwa Biosciences, Replimune, and Amgen; and uncompensated relationships at 
Roche/Genentech and Regeneron Pharmaceuticals, Inc.

Methods
• After a screening period of up to 28 days, patients received cemiplimab 

350 mg every 3 weeks for 93 weeks, followed by four 12-week cycles 
or until disease progression, unacceptable toxicity, or withdrawal of 
consent (Figure 1).

• Inclusion and exclusion criteria are provided in Table 1. 

Results
Patient demographics and baseline characteristics
• As of data cutoff (May 20, 2021), 54 patients were enrolled; median age 

was 63.5 years (range, 38−90) and 70.4% of patients were male  
(Table 2).

• The most common primary tumor sites were the trunk (46.3%) and the 
head and neck (40.7%) (Table 2).

• The most common reasons for discontinuation of HHI therapy were 
progression of disease on HHI (75.9%) or intolerance to HHI (33.3%) 
(Table 2).

Tumor response
• Median duration of follow-up was 8.4 months (range, 1.5–36.2).
• Objective response rate (ORR) per independent central review (ICR) 

was 24.1% (95% confidence interval [CI], 13.5–37.6); with one 
complete response and 12 partial responses (Figure 2, Table 3). 
 - ORR per investigator assessment (INV) was 25.9% (95% CI,  

15.0–39.7), with two complete responses and 12 partial responses.

• Among responders, median time to response was 4.0 months (range, 
2.0−10.5) per ICR.

• Estimated median duration of response (DOR) per ICR was 16.7 months 
(95% CI, 9.8–not evaluable [NE]).

• Median overall survival (OS) was not reached (95% CI, 25.7–NE) 
(Figure 3). The 12-month Kaplan-Meier (KM) estimation of OS was 
84.4% (95% CI, 71.3–91.9).

• Median KM estimation of progression-free survival (PFS) was 8.3 months 
(95% CI, 4.2–15.9) per ICR (Figure 4).

Safety
• The most common treatment-emergent adverse events (TEAEs) of any 

grade were fatigue (42.6%; n=23), diarrhea (37.0%; n=20), constipation 
(22.2%; n=12), and hypertension (20.4%; n=11) (Table 4).

• Immune-related adverse events (irAEs) of any grade occurred in 61.1% 
(n=33) of patients.

• Grade ≥3 irAEs were seen in 9.3% (n=5) of patients; the only Grade ≥3 
irAEs occurring in more than one patient was colitis. 

• Two patients (3.7%) had a serious TEAE resulting in death: 
staphylococcal pneumonia (n=1) and hemoptysis (n=1).

• There were no treatment-related deaths.

†Or by composite response criteria for patient with both visceral and skin lesions. 
BCC, basal cell carcinoma; DOR, duration of response; ICR, independent central review; INV, investigator 
assessment; IV, intravenous; laBCC, locally advanced basal cell carcinoma; ORR, objective response rate;  
OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks; Q9W, every 9 weeks; Q12W, every  
12 weeks; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; WHO, World Health Organization.

Figure 1. Study design

Group 1: Adult patients with metastatic
(nodal and distant) BCC

Group 2: Adult patients with laBCC

Cemiplimab 350 mg IV Q3W
for up to 93 weeks

(or until disease progression, 
unacceptable toxicity, 

or withdrawal of consent)

Tumor assessments
1–5 Q9W, 6–9 Q12W

Tumor response
assessment by ICR 

(RECIST 1.1 for visceral 
lesions or modified WHO 
criteria for skin lesions)†

Primary endpoint: ORR per ICR

Key secondary endpoints: ORR per INV, DOR, 
PFS, OS, complete response per ICR, and safety 
and tolerability.

Table 1. Inclusion and exclusion criteria

Inclusion criteria Exclusion criteria

•  Age ≥18 years 

•   ECOG performance status of 0 or 1

•  Histologically confirmed diagnosis of 
invasive BCC

•   Progression of disease on or 
intolerance to previous HHI  
therapy or having no better than 
stable disease after 9 months on 
HHI therapy

•  At least one measurable baseline 
lesion12

• Ongoing or recent (within 5 years) 
evidence of substantial autoimmune 
disease requiring systemic 
immunosuppression

• Previous treatment with an  
anti–PD-1 or an anti–PD-L1 drug

• Untreated brain metastases that 
may be considered active

• Concurrent malignancy other than 
BCC or history of malignancy other 
than BCC within 3 years of date of 
first planned dose of cemiplimab, 
except for tumors with negligible 
risk of metastasis or death

BCC, basal cell carcinoma; ECOG, Eastern Cooperative Oncology Group; HHI, hedgehog inhibitor;  
PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1.

Table 2. Patient demographic and baseline characteristics

Characteristic mBCC (N=54)

Age, median (range), years 63.5 (38–90)
≥65 years, n (%) 27 (50.0)

Male, n (%) 38 (70.4)
ECOG performance status, n (%)

0 36 (66.7)
1 18 (33.3)

Number of patients with prior HHI therapy, n (%)
Vismodegib 52 (96.3)
Sonidegib 9 (16.7)
Vismodegib + sonidegib 7 (13.0)

Reason for discontinuation of prior HHI, n (%)†

Progression of disease on HHI 41 (75.9)
Intolerant to prior HHI therapy 18 (33.3)

Intolerant to vismodegib 19 (35.2)
Intolerant to sonidegib 5 (9.3)

No better than stable disease after 9 months on HHI therapy 7 (13.0)
Primary tumor site, n (%)

Head and neck 22 (40.7)
Trunk 25 (46.3)
Extremity 6 (11.1)
Anogenital 1 (1.9)

Metastatic status, n (%)
Distant only 19 (35.2)
Distant and nodal 29 (53.7)
Nodal only 5 (9.3)

†Sum is >54 because some patients had more than one reason for discontinuation.
ECOG, Eastern Cooperative Oncology Group; HHI, hedgehog inhibitor; mBCC, metastatic basal cell carcinoma. 

Figure 2. Time to and duration of response in responding patients per ICR

Each horizontal bar represents one patient. A gray arrow indicates a patient still on study. Patients with confirmed 
complete response after a minimum of 48 weeks of treatment could elect to discontinue treatment and continue with all 
relevant study assessments.

ICR, independent central review; mBCC, metastatic basal cell carcinoma.

P
a

ti
e

n
ts

 w
it

h
 r

e
s
p

o
n

s
e

 (
n

=
1
3
)

Month

Patients with mBCC

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44

Complete response
Partial response
Stable disease
Progressive disease
Unable to evaluate
Ongoing treatment 
On study

Figure 3. KM curve for OS

KM, Kaplan-Meier; mBCC, metastatic basal cell carcinoma; OS, overall survival.

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

P
ro

b
a

b
ili

ty
 o

f 
s
u

rv
iv

a
l

Month
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44

Group 1: mBCC
Number of patients at risk

54 53 52 50 44 44 41 35 31 30 26 22 19 17 12 11 8 7 6 2 1 0 0

Figure 4. KM curve for PFS per ICR 

Patients with confirmed complete response after a minimum of 48 weeks of treatment could elect to 
discontinue treatment and continue with all relevant study assessments.
ICR, independent central review; KM, Kaplan-Meier; mBCC, metastatic basal cell carcinoma;  
PFS, progression-free survival.

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0P
ro

b
a

b
ili

ty
 o

f 
p

ro
g

re
s
s
io

n
-f

re
e

 s
u

rv
iv

a
l

Month
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44

Group 1: mBCC
Number of patients at risk

54 50 31 26 24 22 19 10 9 9 4 3 3 2 2 2 1 1 1 0 0 0 0

Table 3. Tumor response per ICR

Response mBCC (N=54)

Best overall response

ORR, % (95% Cl) 24.1 (13.5–37.6)#

Complete response, n (%) 1 (1.9)

Partial response, n (%) 12 (22.2)

Stable disease, n (%) 16 (29.6)

Non-complete response/non-progressive disease, n (%) 5 (9.3)

Progressive disease, n (%) 16 (29.6)

NE,† n (%) 4 (7.4)

Disease control rate, % (95% CI)‡ 63.0 (48.7–75.7)

Durable disease control rate, % (95% CI)§ 42.6 (29.2–56.8)

Time to response, median (range), months¶ 4.0 (2.0–10.5)

KM estimation of DOR, median (95% CI), months 16.7 (9.8−NE)

6 months 100 (NE–NE)

12 months 53.5 (21.2−77.7)

KM estimation of PFS, median (95% CI), months 8.3 (4.2–15.9)
†NE response includes missing and unknown tumor response.
‡Defined as the proportion of patients with complete response, partial response, stable disease or non-complete 
response/non-progressive disease.
§Defined as the proportion of patients with complete response, partial response, stable disease, or non-complete 
response/non-progressive disease for ≥182 days without progressive disease.
¶Data shown are for patients with response.
#ORR per investigator assessment was 25.9% (15.0–39.7).  
CI, confidence interval; DOR, duration of response; ICR, independent central review; KM, Kaplan-Meier; 
mBCC, metastatic basal cell carcinoma; NE, not evaluable; ORR, objective response rate;  
PFS, progression-free survival.

Table 4. TEAEs regardless of attribution†

mBCC (N=54)
n (%) Any grade Grade ≥3
Any TEAE 51 (94.4) 23 (42.6)
Serious TEAEs 16 (29.6) 15 (27.8)
TEAEs leading to treatment discontinuation 4 (7.4) 3 (5.6)
TEAEs associated with an outcome of death‡ 2 (3.7) 2 (3.7)
Any TEAE occurring in ≥10% patients§ 

Fatigue 23 (42.6) 0
Diarrhea 20 (37.0) 0
Constipation 12 (22.2) 0
Hypertension 11 (20.4) 6 (11.1)
Arthralgia 9 (16.7) 0
Pruritus 8 (14.8) 0
Pyrexia 8 (14.8) 1 (1.9)
Weight increased 8 (14.8) 0
Vomiting 7 (13.0) 0
Edema peripheral 6 (11.1) 0
Pain in extremity 6 (11.1) 1 (1.9)
Decreased appetite 6 (11.1) 1 (1.9)
Headache 6 (11.1) 1 (1.9)
Nausea 6 (11.1) 0
Anemia 6 (11.1) 0
Hyperglycemia 6 (11.1) 1 (1.9)

†Adverse events were coded according to the Preferred Terms of the Medical Dictionary for Regulatory Activities, 
version 22.1.  
The severity of adverse events was graded according to National Cancer Institute Common Terminology 
Criteria for Adverse Events, version 4.03.
‡Adverse events leading to death were staphylococcal pneumonia and hemoptysis, deemed unrelated  
to treatment.
§Events are listed in descending order of frequency in any grade.
mBCC, metastatic basal cell carcinoma; TEAE, treatment-emergent adverse event.

Scan the QR 
code for co-author 

disclosures