PD-1 in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03132636
• Collaborator: Sanofi (Industry)
• Enrollment: 138
• Locations: 71
• Arms: 2
• Anticipated Duration (Months): 71
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective is to estimate the objective response rate (ORR) for metastatic Basal Cell Carcinoma (BCC) (group 1) and for unresectable locally advanced BCC (group 2) when treated with cemiplimab as a monotherapy

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Basal Cell	Drug: cemiplimab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1, in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy
• Actual Study Start Date: Jun 29, 2017
• Actual Primary Completion Date: May 20, 2021
• Anticipated Study Completion Date: May 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1- metastatic BCC Administration of cemiplimab in accordance with protocol dosing regimen	Drug: cemiplimab; Regimen as per protocol; Other Names: REGN2810 Libtayo
Experimental: Group 2 - unresectable locally advanced BCC Administration of cemiplimab in accordance with protocol dosing regimen	Drug: cemiplimab; Regimen as per protocol; Other Names: REGN2810 Libtayo

Outcome Measures

Primary Outcome Measures

1. Objective Response Rates (ORR) as Assessed by Independent Central Review (ICR) [Up to 1422 days]

   ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 assessed as per ICR assessment. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm) (< 1 centimeter [cm]). PR: At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. ORR was determined by Clopper-Pearson method.

Secondary Outcome Measures

1. Duration of Response (DOR) Per ICR [Up to 40 months]

   DOR per ICR was determined for participants with best overall response of CR or PR. DOR was measured from the time measurement criteria are first met for CR/PR (whichever was first recorded) until the first date of recurrent or progressive disease (PD) (photographic or radiographic), or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). DOR was determined by Kaplan-Meier estimate.

2. Duration of Response (DOR) Per Investigator Assessment [Up to 40 months]

   DOR per investigator assessment was determined for participants with best overall response of CR or PR. DOR was measured from the time measurement criteria are first met for CR/PR (whichever was first recorded) until the first date of recurrent or progressive disease (PD) (photographic or radiographic), or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). DOR was determined by Kaplan-Meier estimate.

3. Progression Free Survival (PFS) Determined by ICR [Up to 40 months]

   PFS was defined as the time from start of treatment until the first date of recurrent or PD (photographic or radiographic), or death due to any cause, whichever occurred first, was determined by IRC. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). PFS was determined by Kaplan-Meier estimate.

4. Progression Free Survival (PFS) Determined by Investigator Assessment [Up to 40 months]

   PFS was defined as the time from start of treatment until the first date of recurrent or PD (photographic or radiographic), or death due to any cause, whichever occurred first, was determined by IRC. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). PFS was determined by Kaplan-Meier estimate.

5. Overall Survival (OS) [Up to 40 months]

   OS was measured as time from the start of treatment until death due to any cause. Participants who do not die was censored at the last date that participant was documented to be alive. OS was calculated based on Kaplan-Meier method.

6. Percentage of Participants With Complete Response (CR) Rate Assessed by ICR [Up to 1422 days]

   CR rate by ICR was determined by the percentage of participants with best overall response of CR. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm).

7. Change From Baseline of Patient-reported Outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])]

   The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall QoL in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a higher score indicates higher ("better") quality of life/functioning and a positive change from baseline indicates improvement. For the symptom scales/items, a higher score indicates a higher ("worse") level of symptoms/problems, and a negative change from baseline indicates improvement.

8. Change From Baseline of Patient-reported Outcomes in Skindex-16 Questionnaire [Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])]

   Skindex-16 questionnaire contains 16 questions related to quality of life in cancer participants. It consisted of a short 16-item assessment completed by the participant, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Symptoms scale score was an average of items 1 to 4 expressed in a linear scale from 0 to 100, Emotions scale score was an average of items 5 to 11 expressed in a linear scale from 0 to 100 and Functioning scale score was an average of items 12 to 16 expressed in a linear scale from 0 to 100. A negative change from baseline indicates an improvement in the participants condition compared to the baseline.

9. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [Up to 1422 days]

   An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as AEs that developed or worsened during the on-treatment period and treatment-related AEs that occur during post-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.

10. Serum Concentration at End of Infusion (Cmax) of Cemiplimab [At end-of-infusion (within 10 minutes after the end of infusion) on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle of 9 weeks)]

    Cmax of cemiplimab was reported.

11. Serum Concentration at Pre-infusion (Ctrough) of Cemiplimab [At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks)]

    Ctrough of cemiplimab was reported.

12. Number of Participants With Anti-Drug Antibody (ADA) Status [Cycle 1: Days 1 and 43; Cycles 3 and 5: Day 1 (Each cycle of 9 weeks)]

    Immunogenicity was characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the cemiplimab ADA assay post first dose when baseline results = negative or missing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Confirmed diagnosis of invasive BCC

• Progression of disease on hedgehog inhibitor (HHI) therapy or intolerance of prior HHI therapy

• At least 1 measurable lesion

• ≥18 years of age

• Hepatic function, renal function, bone marrow function in defined lab-value-ranges

• Anticipated life expectancy >12 weeks

• Consent to provide archived tumor biopsy material (all patients)

• Group 2: consent to undergo research biopsies

• Group 2: must not be a candidate for radiation therapy or surgery

• Comply with study procedures and site visits

• Sign Subject Information Sheet and Informed Consent Form

Key Exclusion Criteria:

• Ongoing or recent significant autoimmune disease

• Prior treatment with specific pathway-blockers (PD-1/PD-L1)

• Prior treatment with immune-modulating agents within 28 days before cemiplimab

• Untreated brain metastasis that may be considered active

• Immunosuppressive corticosteroid doses (>10mg prednisone) within 28 days prior to treatment with cemiplimab

• Active infections requiring therapy, including HIV, hepatitis

• Pneumonitis within the last 5 years

• Cancer treatment other than radiation therapy, including investigational or standard of care, within 30 days prior to treatment with cemiplimab

• Documented allergic reactions or similar to antibody treatments

• Concurrent malignancies other than BCC, other than those with negligible risk of metastases or death

• Any acute or chronic psychiatric problems

• Having received a solid organ transplantation

• Inability to undergo contrast radiological assessments

• Breastfeeding, pregnant, women of childbearing potential not using contraception

Note: Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Arizona Cancer Centre at Dignity Health	Phoenix	Arizona	United States	85004
2	Mayo Clinic Arizona - Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
3	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Stanford Medicine Outpatient Center - Stanford Dermatology Clinic-Stanford University School of Medicine	Redwood City	California	United States	94063-3132
5	UCSF Helen Dillion Family Cancer Care Center	San Francisco	California	United States	94115
6	University of Colorado Hospital, Anschutz Outpatient Pavilion	Denver	Colorado	United States	80045
7	Mount Sinai Comprehensive Cancer Center	Miami	Florida	United States	33140
8	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
9	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
10	Norton Cancer Institute	Louisville	Kentucky	United States	40202
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	Atlantic Health System / Morristown Medical Center	Morristown	New Jersey	United States	07962
15	Overlook Medical Center	Summit	New Jersey	United States	07901
16	New York University School Of Medicine, Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
17	Mount Sinai Hospital	New York	New York	United States	10029
18	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
19	James Cancer Hospital and Solove Research Institute	Columbus	Ohio	United States	43210
20	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
21	Clinical Research Center of the Carolinas	Charleston	South Carolina	United States	29407
22	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
23	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
24	LKH - Universitaetsklinikum Graz	Graz	Steiermark	Austria	8036
25	Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Dermatologie, Venerologie und Allergologie	Innsbruck		Austria	6020
26	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
27	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
28	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
29	Odette Cancer Center-Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
30	University Health Network	Toronto	Ontario	Canada	M5G 2M9
31	London Regional Cancer Program, London Hsc	Toronto	Ontario	Canada	N6A 4L6
32	CHU de Dijon - Hopital du Bocage	Dijon	Cedex	France	21000
33	Hopital Saint Louis	Paris	Europe	France	75010
34	Centre Hospitalier Lyon-Sud -Hospices Civils de Lyon Groupement Hospitalier Sud	Pierre Benite Cedex	Paris	France	69495
35	Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Saint-André - Hôpital Saint-André	Bordeaux		France	33000
36	Hopital Ambroise Pare	Boulogne Billancourt		France	92100
37	Centre Hospitalier Universitaire de Grenoble	La Tronche		France	38700
38	Hopital Huriez - CHRU de Lille	Lille Cedex		France	59037
39	Centre Leon-Berard (CLB)	Lyon		France	69008
40	CHU Hotel Dieu	Nantes		France	44093
41	Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle	Rouen cedex		France	76031
42	Institut Claudius Regaud	Toulouse Cedex		France	31059
43	Institut Gustave Roussy	Villejuif Cedex		France	94805
44	University Hospital Frankfurt	Frankfurt	Hessen/Germany	Germany	60590
45	Hauttumorcentrum der Charite (HTCC)-Charite Universitatsmedizin Berlin	Berlin		Germany	C-10117
46	Elbekliniken Buxtehude	Buxtehude		Germany	21614
47	University Hospital Dresden	Dresden		Germany	01307
48	Universitaetsklinik Essen	Essen		Germany	45147
49	SRH Wald-Kliniken Gera GmbH	Gera		Germany	07548
50	Hannover Medical School	Hannover		Germany	30625
51	NCT Dermatoonkologie	Heidelberg		Germany	69120
52	University of Kiel	Kiel		Germany	24105
53	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz		Germany	55131
54	Klinik Fur Dermatologie Und Allergollogie	Quedlinburg		Germany	06484
55	University Hospital Tubingen	Tübingen		Germany	72076
56	National and Kapodistrian University of Athens - School of Health Sciences - Faculty of Medicine	Athens		Greece	115 27
57	National and Kapodistrian University of Athens - School of Health Sciences	Athens		Greece	11527
58	Andreas Sygros Hosptial-University of Athen	Athens		Greece	16121
59	University General Hospital of Ioannina - Dermatology and Venereology Department	Ioánnina		Greece	45110
60	Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna	Bologna	Bo	Italy	40138
61	Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia	Brescia	Province Of Brescia	Italy	25123
62	U.O.Dermatologia Azienda Sanitaria Firenze Universita' Firenze	Firenze		Italy	50132
63	University L'Aquila	L'Aquila		Italy	67100
64	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
65	U.O.S.C Di Oncologia Medica E Terapie Innovative	Napoli		Italy	80131
66	Catholic University of the S.Heart	Roma		Italy	168
67	Catalan Institute of Oncology Badalona	Badalona		Spain	08916
68	Hospital Clinic I Provincialde Barcelona	Barcelona		Spain	08036
69	Hospital Universitario de Torrejon	Madrid		Spain	28850
70	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
71	University Hospital Zurich Usz	Zürich		Switzerland	8091

Sponsors and Collaborators

• Regeneron Pharmaceuticals
• Sanofi

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jul 29, 2019
• Statistical Analysis Plan - Feb 7, 2020

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03132636
• Other Study ID Numbers: R2810-ONC-1620; 2016-003122-16
• First Posted: Apr 28, 2017
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Basal Cell; Cemiplimab

Study Results

Participant Flow

Pre-assignment Detail

138 of the 170 screened participants, were enrolled & treated. Eligible participants were enrolled into 2 groups. Group 1: participants with metastatic Basal Cell Carcinoma (mBCC). Group 2: participants with unresectable locally advanced BCC (laBCC) who experienced progression of disease on Hedgehog inhibitor (HHI) therapy, or response no better than stable disease for at least 9 months or were intolerant of prior HHI therapy. Results presented here based on primary analysis cut-off (20May2021).

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Period Title: Overall Study
STARTED	54	84
COMPLETED	1	9
NOT COMPLETED	53	75

Baseline Characteristics

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)	Total
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.	Total of all reporting groups
Overall Participants	54	84	138
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.8 (11.09)	69.1 (12.84)	67.0 (12.42)
Sex: Female, Male (Count of Participants)
Female	16 29.6%	28 33.3%	44 31.9%
Male	38 70.4%	56 66.7%	94 68.1%
Race/Ethnicity, Customized (Number) [Number]
Race : White	47 87%	57 67.9%	104 75.4%
Race : Not Reported	1 1.9%	0 0%	1 0.7%
Race : Missing	6 11.1%	27 32.1%	33 23.9%
Race/Ethnicity, Customized (Number) [Number]
Ethnicity : Not Hispanic or Latino	46 85.2%	56 66.7%	102 73.9%
Ethnicity : Hispanic or Latino	2 3.7%	1 1.2%	3 2.2%
Ethnicity : Missing	6 11.1%	27 32.1%	33 23.9%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rates (ORR) as Assessed by Independent Central Review (ICR)
Description	ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 assessed as per ICR assessment. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm) (< 1 centimeter [cm]). PR: At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. ORR was determined by Clopper-Pearson method.
Time Frame	Up to 1422 days

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	54	84
Number (95% Confidence Interval) [Percentage of Participants]	24.1 44.6%	32.1 38.2%

2. Secondary Outcome

Title	Duration of Response (DOR) Per ICR
Description	DOR per ICR was determined for participants with best overall response of CR or PR. DOR was measured from the time measurement criteria are first met for CR/PR (whichever was first recorded) until the first date of recurrent or progressive disease (PD) (photographic or radiographic), or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). DOR was determined by Kaplan-Meier estimate.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	13	27
Median (95% Confidence Interval) [Months]	16.7	NA

3. Secondary Outcome

Title	Duration of Response (DOR) Per Investigator Assessment
Description	DOR per investigator assessment was determined for participants with best overall response of CR or PR. DOR was measured from the time measurement criteria are first met for CR/PR (whichever was first recorded) until the first date of recurrent or progressive disease (PD) (photographic or radiographic), or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). DOR was determined by Kaplan-Meier estimate.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	14	31
Median (95% Confidence Interval) [Months]	19.3	19.6

4. Secondary Outcome

Title	Progression Free Survival (PFS) Determined by ICR
Description	PFS was defined as the time from start of treatment until the first date of recurrent or PD (photographic or radiographic), or death due to any cause, whichever occurred first, was determined by IRC. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). PFS was determined by Kaplan-Meier estimate.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	34	46
Median (95% Confidence Interval) [Months]	8.3	16.5

5. Secondary Outcome

Title	Progression Free Survival (PFS) Determined by Investigator Assessment
Description	PFS was defined as the time from start of treatment until the first date of recurrent or PD (photographic or radiographic), or death due to any cause, whichever occurred first, was determined by IRC. PD: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). PFS was determined by Kaplan-Meier estimate.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	41	52
Median (95% Confidence Interval) [Months]	6.6	17.1

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was measured as time from the start of treatment until death due to any cause. Participants who do not die was censored at the last date that participant was documented to be alive. OS was calculated based on Kaplan-Meier method.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	54	84
Median (95% Confidence Interval) [Months]	NA	NA

7. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) Rate Assessed by ICR
Description	CR rate by ICR was determined by the percentage of participants with best overall response of CR. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm).
Time Frame	Up to 1422 days

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	54	84
Number (95% Confidence Interval) [Percentage of Participants]	1.9 3.5%	7.1 8.5%

8. Secondary Outcome

Title	Change From Baseline of Patient-reported Outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Description	The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall QoL in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a higher score indicates higher ("better") quality of life/functioning and a positive change from baseline indicates improvement. For the symptom scales/items, a higher score indicates a higher ("worse") level of symptoms/problems, and a negative change from baseline indicates improvement.
Time Frame	Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specific time points.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	43	75
Physical Functioning: Change at Cycle 2 Day 1	-4.88 (14.274)	-1.55 (12.101)
Physical Functioning: Change at Cycle 3 Day 1	-1.78 (13.481)	-0.56 (15.947)
Physical Functioning: Change at Cycle 4 Day 1	-6.60 (12.828)	-3.79 (17.814)
Physical Functioning: Change at Cycle 5 Day 1	1.08 (10.033)	-2.86 (17.063)
Physical Functioning: Change at Cycle 6 Day 1	-1.67 (9.734)	0.33 (12.073)
Physical Functioning: Change at Cycle 7 Day 1	-0.38 (11.142)	-0.20 (15.410)
Physical Functioning: Change at Cycle 8 Day 1	-3.33 (12.344)	-3.03 (13.549)
Physical Functioning: Change at Cycle 9 Day 1	-1.83 (9.110)	-5.06 (20.444)
Role Functioning: Change at Cycle 2 Day 1	-2.71 (27.442)	-3.11 (20.264)
Role Functioning: Change at Cycle 3 Day 1	5.17 (27.854)	-4.87 (25.297)
Role Functioning: Change at Cycle 4 Day 1	-3.21 (25.394)	-6.06 (26.326)
Role Functioning: Change at Cycle 5 Day 1	5.00 (22.361)	-5.33 (26.393)
Role Functioning: Change at Cycle 6 Day 1	6.14 (21.667)	-3.33 (16.963)
Role Functioning: Change at Cycle 7 Day 1	12.82 (24.677)	-7.07 (16.682)
Role Functioning: Change at Cycle 8 Day 1	10.42 (19.796)	-4.04 (19.557)
Role Functioning: Change at Cycle 9 Day 1	10.00 (23.831)	-9.77 (30.052)
Emotional Functioning: Change at Cycle 2 Day 1	3.17 (19.638)	1.95 (20.483)
Emotional Functioning: Change at Cycle 3 Day 1	1.15 (18.730)	1.56 (18.538)
Emotional Functioning: Change at Cycle 4 Day 1	3.53 (22.007)	1.39 (21.277)
Emotional Functioning: Change at Cycle 5 Day 1	5.83 (24.046)	-4.59 (19.622)
Emotional Functioning: Change at Cycle 6 Day 1	7.02 (20.650)	1.04 (19.809)
Emotional Functioning: Change at Cycle 7 Day 1	3.85 (18.199)	-4.63 (19.576)
Emotional Functioning: Change at Cycle 8 Day 1	20.37 (26.389)	3.11 (19.810)
Emotional Functioning: Change at Cycle 9 Day 1	5.83 (18.023)	2.11 (17.246)
Cognitive Functioning: Change at Cycle 2 Day 1	0.78 (13.586)	-2.48 (26.985)
Cognitive Functioning: Change at Cycle 3 Day 1	-1.72 (16.871)	-4.17 (23.382)
Cognitive Functioning: Change at Cycle 4 Day 1	-0.64 (15.261)	-4.94 (21.385)
Cognitive Functioning: Change at Cycle 5 Day 1	-4.17 (14.178)	-6.46 (25.188)
Cognitive Functioning: Change at Cycle 6 Day 1	-0.88 (12.998)	-1.25 (19.017)
Cognitive Functioning: Change at Cycle 7 Day 1	-2.56 (11.479)	-5.56 (18.942)
Cognitive Functioning: Change at Cycle 8 Day 1	-7.41 (12.108)	1.52 (17.362)
Cognitive Functioning: Change at Cycle 9 Day 1	-11.67 (26.117)	-2.30 (23.873)
Social Functioning: Change at Cycle 2 Day 1	0.39 (19.412)	4.50 (21.422)
Social Functioning: Change at Cycle 3 Day 1	3.45 (16.891)	0.78 (21.088)
Social Functioning: Change at Cycle 4 Day 1	3.85 (24.179)	1.85 (23.272)
Social Functioning: Change at Cycle 5 Day 1	3.33 (22.685)	0.34 (23.445)
Social Functioning: Change at Cycle 6 Day 1	10.53 (16.860)	0.00 (24.749)
Social Functioning: Change at Cycle 7 Day 1	12.82 (22.724)	0.00 (18.162)
Social Functioning: Change at Cycle 8 Day 1	12.96 (16.197)	2.02 (23.848)
Social Functioning: Change at Cycle 9 Day 1	10.00 (14.055)	-2.30 (27.359)
Fatigue: Change at Cycle 2 Day 1	5.17 (22.919)	6.44 (24.542)
Fatigue: Change at Cycle 3 Day 1	1.92 (18.322)	6.58 (24.901)
Fatigue: Change at Cycle 4 Day 1	-2.56 (21.154)	7.58 (25.912)
Fatigue: Change at Cycle 5 Day 1	-5.56 (24.048)	9.67 (23.404)
Fatigue: Change at Cycle 6 Day 1	-5.85 (19.376)	7.78 (17.649)
Fatigue: Change at Cycle 7 Day 1	-1.71 (19.692)	14.14 (20.838)
Fatigue: Change at Cycle 8 Day 1	-12.50 (22.567)	9.09 (19.534)
Fatigue: Change at Cycle 9 Day 1	-1.11 (16.932)	12.64 (20.080)
Nausea/Vomiting: Change at Cycle 2 Day 1	-0.78 (8.095)	0.22 (12.703)
Nausea/Vomiting: Change at Cycle 3 Day 1	0.00 (13.363)	-1.79 (12.884)
Nausea/Vomiting: Change at Cycle 4 Day 1	0.00 (16.330)	0.30 (13.414)
Nausea/Vomiting: Change at Cycle 5 Day 1	0.83 (10.080)	1.00 (13.640)
Nausea/Vomiting: Change at Cycle 6 Day 1	-0.88 (3.824)	1.67 (13.503)
Nausea/Vomiting: Change at Cycle 7 Day 1	-1.28 (14.372)	3.03 (13.472)
Nausea/Vomiting: Change at Cycle 8 Day 1	0.00 (0.000)	0.51 (12.832)
Nausea/Vomiting: Change at Cycle 9 Day 1	0.00 (0.000)	-2.30 (13.890)
Pain: Change at Cycle 2 Day 1	-2.33 (30.338)	-0.22 (26.351)
Pain: Change at Cycle 3 Day 1	-9.77 (22.056)	-1.54 (30.151)
Pain: Change at Cycle 4 Day 1	0.00 (29.439)	-4.85 (25.795)
Pain: Change at Cycle 5 Day 1	-4.17 (25.291)	-4.00 (25.098)
Pain: Change at Cycle 6 Day 1	-14.04 (29.535)	-2.92 (24.427)
Pain: Change at Cycle 7 Day 1	-21.79 (29.174)	-4.04 (24.661)
Pain: Change at Cycle 8 Day 1	-14.81 (28.191)	-7.58 (25.716)
Pain: Change at Cycle 9 Day 1	-21.67 (28.382)	-5.17 (24.030)
Dyspnoea: Change at Cycle 2 Day 1	2.38 (17.097)	1.33 (24.162)
Dyspnoea: Change at Cycle 3 Day 1	3.57 (16.578)	-0.51 (23.930)
Dyspnoea: Change at Cycle 4 Day 1	0.00 (16.667)	2.42 (24.724)
Dyspnoea: Change at Cycle 5 Day 1	3.51 (21.928)	0.00 (28.054)
Dyspnoea: Change at Cycle 6 Day 1	1.85 (13.873)	-1.67 (19.900)
Dyspnoea: Change at Cycle 7 Day 1	2.78 (30.011)	2.02 (21.952)
Dyspnoea: Change at Cycle 8 Day 1	8.33 (23.570)	2.02 (21.952)
Dyspnoea: Change at Cycle 9 Day 1	7.41 (27.778)	2.30 (17.663)
Insomnia: Change at Cycle 2 Day 1	-2.33 (26.622)	0.44 (24.195)
Insomnia: Change at Cycle 3 Day 1	-6.90 (24.200)	-0.51 (26.016)
Insomnia: Change at Cycle 4 Day 1	-10.26 (29.468)	-1.82 (19.687)
Insomnia: Change at Cycle 5 Day 1	-15.00 (31.484)	1.33 (30.087)
Insomnia: Change at Cycle 6 Day 1	-17.54 (32.142)	-4.17 (24.093)
Insomnia: Change at Cycle 7 Day 1	-7.69 (41.172)	1.01 (28.241)
Insomnia: Change at Cycle 8 Day 1	-25.00 (52.705)	3.03 (25.500)
Insomnia: Change at Cycle 9 Day 1	-6.67 (40.976)	5.75 (25.306)
Appetite loss: Change at Cycle 2 Day 1	4.65 (26.807)	-2.25 (27.215)
Appetite loss: Change at Cycle 3 Day 1	-2.30 (15.252)	-4.30 (22.163)
Appetite loss: Change at Cycle 4 Day 1	-1.28 (30.523)	-3.09 (26.117)
Appetite loss: Change at Cycle 5 Day 1	3.33 (21.357)	-1.36 (30.398)
Appetite loss: Change at Cycle 6 Day 1	-1.75 (17.476)	-2.56 (29.004)
Appetite loss: Change at Cycle 7 Day 1	-5.13 (12.518)	-1.01 (30.601)
Appetite loss: Change at Cycle 8 Day 1	-4.17 (11.785)	-2.08 (31.609)
Appetite loss: Change at Cycle 9 Day 1	-3.33 (18.922)	1.19 (30.741)
Constipation: Change at Cycle 2 Day 1	1.55 (19.181)	2.25 (21.603)
Constipation: Change at Cycle 3 Day 1	0.00 (21.822)	1.06 (20.712)
Constipation: Change at Cycle 4 Day 1	-2.56 (18.674)	1.23 (21.440)
Constipation: Change at Cycle 5 Day 1	5.00 (16.312)	-0.68 (22.037)
Constipation: Change at Cycle 6 Day 1	0.00 (15.713)	-1.67 (18.413)
Constipation: Change at Cycle 7 Day 1	5.13 (18.490)	4.04 (13.838)
Constipation: Change at Cycle 8 Day 1	8.33 (15.430)	-2.02 (16.540)
Constipation: Change at Cycle 9 Day 1	0.00 (15.713)	1.15 (22.683)
Diarrhea: Change at Cycle 2 Day 1	3.88 (14.924)	0.45 (24.360)
Diarrhea: Change at Cycle 3 Day 1	1.15 (14.037)	-1.04 (20.547)
Diarrhea: Change at Cycle 4 Day 1	3.85 (23.715)	-1.85 (19.870)
Diarrhea: Change at Cycle 5 Day 1	6.67 (20.520)	-0.68 (23.064)
Diarrhea: Change at Cycle 6 Day 1	3.51 (18.904)	-1.67 (18.413)
Diarrhea: Change at Cycle 7 Day 1	0.00 (13.608)	1.01 (19.516)
Diarrhea: Change at Cycle 8 Day 1	3.70 (11.111)	-1.01 (19.516)
Diarrhea: Change at Cycle 9 Day 1	3.33 (10.541)	-2.30 (21.696)
Financial Problems: Change at Cycle 2 Day 1	-3.10 (17.539)	-3.15 (25.385)
Financial Problems: Change at Cycle 3 Day 1	0.00 (18.144)	-4.23 (24.313)
Financial Problems: Change at Cycle 4 Day 1	-5.13 (22.494)	-4.94 (23.710)
Financial Problems: Change at Cycle 5 Day 1	0.00 (18.732)	-6.80 (22.546)
Financial Problems: Change at Cycle 6 Day 1	-1.75 (23.501)	-5.83 (27.099)
Financial Problems: Change at Cycle 7 Day 1	-2.56 (21.350)	1.01 (19.516)
Financial Problems: Change at Cycle 8 Day 1	-3.70 (20.031)	1.01 (19.516)
Financial Problems: Change at Cycle 9 Day 1	-10.00 (16.102)	-2.30 (23.454)
Global health status/QoL: Change at Cycle 2 Day 1	-3.68 (21.845)	2.55 (15.298)
Global health status/QoL: Change at Cycle 3 Day 1	3.74 (14.362)	-2.55 (19.823)
Global health status/QoL: Change at Cycle 4 Day 1	-2.24 (14.636)	-0.49 (18.136)
Global health status/QoL: Change at Cycle 5 Day 1	7.50 (14.023)	-1.91 (21.210)
Global health status/QoL: Change at Cycle 6 Day 1	10.96 (11.802)	4.17 (19.447)
Global health status/QoL: Change at Cycle 7 Day 1	16.03 (22.428)	-3.13 (19.715)
Global health status/QoL: Change at Cycle 8 Day 1	7.41 (14.096)	2.15 (21.727)
Global health status/QoL: Change at Cycle 9 Day 1	6.67 (20.713)	-7.14 (28.211)

9. Secondary Outcome

Title	Change From Baseline of Patient-reported Outcomes in Skindex-16 Questionnaire
Description	Skindex-16 questionnaire contains 16 questions related to quality of life in cancer participants. It consisted of a short 16-item assessment completed by the participant, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Symptoms scale score was an average of items 1 to 4 expressed in a linear scale from 0 to 100, Emotions scale score was an average of items 5 to 11 expressed in a linear scale from 0 to 100 and Functioning scale score was an average of items 12 to 16 expressed in a linear scale from 0 to 100. A negative change from baseline indicates an improvement in the participants condition compared to the baseline.
Time Frame	Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])

Outcome Measure Data

Analysis Population Description

The FAS included all enrolled participants for each group who passed screening and were deemed to be eligible for this study. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specific time points.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	42	71
Emotions: Change at Cycle 2 Day 1	-6.90 (24.422)	-8.93 (27.767)
Emotions: Change at Cycle 3 Day 1	-7.92 (18.033)	-8.60 (25.641)
Emotions: Change at Cycle 4 Day 1	-3.97 (17.175)	-11.45 (24.215)
Emotions: Change at Cycle 5 Day 1	-0.14 (12.835)	-10.25 (24.646)
Emotions: Change at Cycle 6 Day 1	-9.08 (22.824)	-19.73 (27.304)
Emotions: Change at Cycle 7 Day 1	6.55 (17.053)	-13.65 (27.132)
Emotions: Change at Cycle 8 Day 1	2.38 (5.247)	-13.97 (25.001)
Emotions: Change at Cycle 9 Day 1	8.17 (12.868)	-15.08 (31.843)
Symptoms: Change at Cycle 2 Day 1	0.99 (18.788)	-1.31 (21.607)
Symptoms: Change at Cycle 3 Day 1	3.85 (16.580)	-0.26 (24.158)
Symptoms: Change at Cycle 4 Day 1	5.30 (18.464)	-6.62 (23.917)
Symptoms: Change at Cycle 5 Day 1	-0.98 (15.205)	-4.11 (18.062)
Symptoms: Change at Cycle 6 Day 1	-1.56 (16.307)	-1.85 (21.419)
Symptoms: Change at Cycle 7 Day 1	4.17 (23.233)	0.69 (24.518)
Symptoms: Change at Cycle 8 Day 1	6.77 (18.222)	-2.96 (24.395)
Symptoms: Change at Cycle 9 Day 1	10.42 (21.178)	-3.42 (24.455)
Functioning: Change at Cycle 2 Day 1	-3.49 (19.183)	-4.98 (23.650)
Functioning: Change at Cycle 3 Day 1	-5.00 (18.166)	-4.76 (20.203)
Functioning: Change at Cycle 4 Day 1	-8.18 (24.119)	-5.82 (23.275)
Functioning: Change at Cycle 5 Day 1	-7.06 (20.746)	-3.76 (16.369)
Functioning: Change at Cycle 6 Day 1	-12.08 (27.022)	-11.14 (18.113)
Functioning: Change at Cycle 7 Day 1	-3.89 (19.583)	-6.00 (15.767)
Functioning: Change at Cycle 8 Day 1	-8.33 (26.367)	-7.00 (17.926)
Functioning: Change at Cycle 9 Day 1	-9.67 (22.192)	-5.60 (20.965)

10. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as AEs that developed or worsened during the on-treatment period and treatment-related AEs that occur during post-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.
Time Frame	Up to 1422 days

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) included all enrolled participants who received any study drug for each group.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	54	84
Participants with any TEAEs	51 94.4%	83 98.8%
Participants with any Serious TEAEs	16 29.6%	31 36.9%

11. Secondary Outcome

Title	Serum Concentration at End of Infusion (Cmax) of Cemiplimab
Description	Cmax of cemiplimab was reported.
Time Frame	At end-of-infusion (within 10 minutes after the end of infusion) on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle of 9 weeks)

Outcome Measure Data

Analysis Population Description

The pharmacokinetics (PK) analysis set included all participants who received any cemiplimab and had at least one non-missing post-baseline measurement of cemiplimab concentration in serum. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	30	61
Mean (Standard Deviation) [Milligram per Liter (mg/L)]	160 (52.7)	192 (91.6)

12. Secondary Outcome

Title	Serum Concentration at Pre-infusion (Ctrough) of Cemiplimab
Description	Ctrough of cemiplimab was reported.
Time Frame	At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received any cemiplimab and had at least one non-missing post-baseline measurement of cemiplimab concentration in serum. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	32	66
Mean (Standard Deviation) [mg/L]	60.6 (28.2)	68.6 (32.8)

13. Secondary Outcome

Title	Number of Participants With Anti-Drug Antibody (ADA) Status
Description	Immunogenicity was characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the cemiplimab ADA assay post first dose when baseline results = negative or missing.
Time Frame	Cycle 1: Days 1 and 43; Cycles 3 and 5: Day 1 (Each cycle of 9 weeks)

Outcome Measure Data

Analysis Population Description

The anti-drug antibody set included all participants who received cemiplimab and who had at least 1 non-missing result in the ADA assay after the first dose of the study drug.

Arm/Group Title	Group 1: Metastatic BCC (mBCC)	Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.	Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
Measure Participants	52	81
Negative ADA	50 92.6%	75 89.3%
Pre-Existing ADA	2 3.7%	2 2.4%
Treatment-emergent ADA	0 0%	4 4.8%

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to 1422 days.
Arm/Group Title	Group 1: Metastatic BCC (mBCC)		Group 2: Unresectable Locally Advanced BCC (laBCC)
Arm/Group Description	Participants with metastatic BCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or CR.		Participants with unresectable laBCC received IV infusion of cemiplimab at a dose of 350 mg Q3W for up to 93 weeks of treatment cycles (cycles 1-5 [each cycle of 9 weeks] followed by cycles 6-9 [each cycle of 12 weeks]) or until PD, unacceptable toxicity, withdrawal of consent, or confirmed CR.
All Cause Mortality
	Group 1: Metastatic BCC (mBCC)		Group 2: Unresectable Locally Advanced BCC (laBCC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/54 (29.6%)		17/84 (20.2%)
Serious Adverse Events
	Group 1: Metastatic BCC (mBCC)		Group 2: Unresectable Locally Advanced BCC (laBCC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/54 (29.6%)		32/84 (38.1%)
Blood and lymphatic system disorders
Anaemia	0/54 (0%)	0	2/84 (2.4%)	3
Pancytopenia	1/54 (1.9%)	1	0/84 (0%)	0
Lymphadenopathy mediastinal	1/54 (1.9%)	1	0/84 (0%)	0
Cardiac disorders
Cardiac failure	0/54 (0%)	0	1/84 (1.2%)	1
Autoimmune pericarditis	1/54 (1.9%)	1	0/84 (0%)	0
Myocardial infarction	0/54 (0%)	0	2/84 (2.4%)	2
Supraventricular tachycardia	0/54 (0%)	0	1/84 (1.2%)	1
Acute coronary syndrome	1/54 (1.9%)	1	0/84 (0%)	0
Atrial fibrillation	1/54 (1.9%)	1	0/84 (0%)	0
Autoimmune myocarditis	1/54 (1.9%)	1	0/84 (0%)	0
Immune-mediated myocarditis	1/54 (1.9%)	1	0/84 (0%)	0
Ear and labyrinth disorders
Ear disorder	0/54 (0%)	0	1/84 (1.2%)	1
Endocrine disorders
Adrenal insufficiency	0/54 (0%)	0	2/84 (2.4%)	2
Hypophysitis	0/54 (0%)	0	1/84 (1.2%)	1
Gastrointestinal disorders
Colitis	2/54 (3.7%)	2	2/84 (2.4%)	2
Autoimmune colitis	0/54 (0%)	0	1/84 (1.2%)	1
Constipation	0/54 (0%)	0	1/84 (1.2%)	1
Erosive oesophagitis	0/54 (0%)	0	1/84 (1.2%)	1
General disorders
Pyrexia	1/54 (1.9%)	1	0/84 (0%)	0
Fatigue	0/54 (0%)	0	1/84 (1.2%)	1
General physical health deterioration	1/54 (1.9%)	1	0/84 (0%)	0
Hepatobiliary disorders
Autoimmune hepatitis	1/54 (1.9%)	1	0/84 (0%)	0
Immune-mediated hepatitis	0/54 (0%)	0	1/84 (1.2%)	1
Immune system disorders
Sarcoidosis	0/54 (0%)	0	1/84 (1.2%)	2
Infections and infestations
Urinary tract infection	1/54 (1.9%)	1	4/84 (4.8%)	4
Pneumonia	1/54 (1.9%)	1	0/84 (0%)	0
Infection	1/54 (1.9%)	1	0/84 (0%)	0
Skin infection	1/54 (1.9%)	1	0/84 (0%)	0
Clostridium difficile infection	1/54 (1.9%)	1	0/84 (0%)	0
Hepatitis C	0/54 (0%)	0	1/84 (1.2%)	1
Influenza	0/54 (0%)	0	1/84 (1.2%)	1
Lower respiratory tract infection	0/54 (0%)	0	1/84 (1.2%)	1
Oral candidiasis	0/54 (0%)	0	1/84 (1.2%)	1
Soft tissue infection	0/54 (0%)	0	1/84 (1.2%)	1
Subcutaneous abscess	0/54 (0%)	0	1/84 (1.2%)	1
Wound infection staphylococcal	0/54 (0%)	0	1/84 (1.2%)	1
Arthritis bacterial	1/54 (1.9%)	1	0/84 (0%)	0
Atypical pneumonia	1/54 (1.9%)	1	0/84 (0%)	0
Clostridium difficile colitis	1/54 (1.9%)	1	0/84 (0%)	0
Pneumonia staphylococcal	1/54 (1.9%)	1	0/84 (0%)	0
Injury, poisoning and procedural complications
Radial head dislocation	0/54 (0%)	0	1/84 (1.2%)	1
Upper limb fracture	0/54 (0%)	0	1/84 (1.2%)	1
Fall	1/54 (1.9%)	1	0/84 (0%)	0
Infusion related reaction	1/54 (1.9%)	1	0/84 (0%)	0
Multiple fractures	1/54 (1.9%)	1	0/84 (0%)	0
Procedural pain	1/54 (1.9%)	1	0/84 (0%)	0
Tibia fracture	1/54 (1.9%)	1	0/84 (0%)	0
Wound haemorrhage	1/54 (1.9%)	1	0/84 (0%)	0
Investigations
Weight decreased	0/54 (0%)	0	1/84 (1.2%)	1
Metabolism and nutrition disorders
Cachexia	0/54 (0%)	0	1/84 (1.2%)	2
Musculoskeletal and connective tissue disorders
Back pain	0/54 (0%)	0	1/84 (1.2%)	1
Dupuytren's contracture	0/54 (0%)	0	1/84 (1.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm	0/54 (0%)	0	2/84 (2.4%)	2
Basal cell carcinoma	0/54 (0%)	0	1/84 (1.2%)	1
Brain neoplasm malignant	0/54 (0%)	0	1/84 (1.2%)	1
Meningioma	0/54 (0%)	0	1/84 (1.2%)	1
Lymphoproliferative disorder	1/54 (1.9%)	1	0/84 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/54 (0%)	0	1/84 (1.2%)	1
Brain oedema	0/54 (0%)	0	1/84 (1.2%)	1
Cerebrospinal fluid leakage	0/54 (0%)	0	1/84 (1.2%)	1
Dizziness	0/54 (0%)	0	1/84 (1.2%)	1
Haemorrhage intracranial	0/54 (0%)	0	1/84 (1.2%)	1
Somnolence	1/54 (1.9%)	2	1/84 (1.2%)	1
Facial paralysis	1/54 (1.9%)	1	0/84 (0%)	0
Headache	1/54 (1.9%)	1	0/84 (0%)	0
Psychiatric disorders
Delirium	0/54 (0%)	0	1/84 (1.2%)	1
Renal and urinary disorders
Acute kidney injury	0/54 (0%)	0	2/84 (2.4%)	2
Urinary retention	1/54 (1.9%)	1	0/84 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/54 (1.9%)	1	0/84 (0%)	0
Haemoptysis	1/54 (1.9%)	1	0/84 (0%)	0
Respiratory failure	1/54 (1.9%)	1	0/84 (0%)	0
Pulmonary oedema	0/54 (0%)	0	1/84 (1.2%)	1
Pleural effusion	1/54 (1.9%)	1	0/84 (0%)	0
Skin and subcutaneous tissue disorders
Dermal cyst	0/54 (0%)	0	1/84 (1.2%)	1
Vascular disorders
Hypotension	0/54 (0%)	0	1/84 (1.2%)	1
Hypertensive crisis	0/54 (0%)	0	1/84 (1.2%)	2
Peripheral ischaemia	0/54 (0%)	0	1/84 (1.2%)	1
Phlebitis	0/54 (0%)	0	1/84 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Group 1: Metastatic BCC (mBCC)		Group 2: Unresectable Locally Advanced BCC (laBCC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/54 (92.6%)		75/84 (89.3%)
Blood and lymphatic system disorders
Anaemia	6/54 (11.1%)	7	13/84 (15.5%)	19
Leukocytosis	1/54 (1.9%)	1	7/84 (8.3%)	8
Endocrine disorders
Hypothyroidism	4/54 (7.4%)	4	8/84 (9.5%)	9
Hyperthyroidism	5/54 (9.3%)	7	2/84 (2.4%)	2
Eye disorders
Cataract	0/54 (0%)	0	5/84 (6%)	6
Gastrointestinal disorders
Nausea	6/54 (11.1%)	9	13/84 (15.5%)	19
Vomiting	7/54 (13%)	9	6/84 (7.1%)	10
Constipation	12/54 (22.2%)	14	5/84 (6%)	6
Diarrhoea	20/54 (37%)	27	20/84 (23.8%)	33
Abdominal pain	4/54 (7.4%)	4	6/84 (7.1%)	7
Dry mouth	3/54 (5.6%)	3	3/84 (3.6%)	3
General disorders
Pyrexia	7/54 (13%)	9	5/84 (6%)	7
Asthenia	5/54 (9.3%)	6	17/84 (20.2%)	27
Fatigue	23/54 (42.6%)	31	25/84 (29.8%)	34
Oedema peripheral	6/54 (11.1%)	8	5/84 (6%)	5
Influenza like illness	2/54 (3.7%)	2	5/84 (6%)	7
Pain	3/54 (5.6%)	4	2/84 (2.4%)	2
Infections and infestations
Urinary tract infection	4/54 (7.4%)	5	10/84 (11.9%)	11
Bronchitis	0/54 (0%)	0	6/84 (7.1%)	7
Upper respiratory tract infection	3/54 (5.6%)	3	6/84 (7.1%)	6
Conjunctivitis	0/54 (0%)	0	5/84 (6%)	5
Injury, poisoning and procedural complications
Fall	4/54 (7.4%)	7	5/84 (6%)	5
Infusion related reaction	3/54 (5.6%)	3	0/84 (0%)	0
Investigations
Alanine aminotransferase increased	3/54 (5.6%)	3	4/84 (4.8%)	6
Blood creatinine increased	4/54 (7.4%)	4	8/84 (9.5%)	9
Weight decreased	5/54 (9.3%)	6	7/84 (8.3%)	7
Blood creatine phosphokinase increased	4/54 (7.4%)	5	6/84 (7.1%)	8
Weight increased	8/54 (14.8%)	12	2/84 (2.4%)	2
Metabolism and nutrition disorders
Decreased appetite	6/54 (11.1%)	6	14/84 (16.7%)	18
Hypoalbuminaemia	1/54 (1.9%)	2	5/84 (6%)	11
Hypokalaemia	4/54 (7.4%)	4	4/84 (4.8%)	6
Hyperglycaemia	6/54 (11.1%)	8	2/84 (2.4%)	2
Musculoskeletal and connective tissue disorders
Back pain	5/54 (9.3%)	5	5/84 (6%)	6
Arthralgia	9/54 (16.7%)	10	16/84 (19%)	24
Pain in extremity	6/54 (11.1%)	10	4/84 (4.8%)	5
Muscle spasms	3/54 (5.6%)	3	5/84 (6%)	5
Myalgia	3/54 (5.6%)	4	3/84 (3.6%)	3
Neck pain	4/54 (7.4%)	4	2/84 (2.4%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/54 (1.9%)	1	9/84 (10.7%)	12
Basal cell carcinoma	3/54 (5.6%)	5	7/84 (8.3%)	8
Seborrhoeic keratosis	1/54 (1.9%)	1	5/84 (6%)	5
Nervous system disorders
Headache	6/54 (11.1%)	7	12/84 (14.3%)	14
Dizziness	5/54 (9.3%)	5	7/84 (8.3%)	8
Psychiatric disorders
Anxiety	3/54 (5.6%)	3	3/84 (3.6%)	3
Renal and urinary disorders
Haematuria	4/54 (7.4%)	5	3/84 (3.6%)	3
Respiratory, thoracic and mediastinal disorders
Cough	4/54 (7.4%)	5	10/84 (11.9%)	14
Dyspnoea	4/54 (7.4%)	5	11/84 (13.1%)	17
Skin and subcutaneous tissue disorders
Rash	4/54 (7.4%)	4	6/84 (7.1%)	6
Pruritus	8/54 (14.8%)	13	20/84 (23.8%)	24
Dry skin	5/54 (9.3%)	6	7/84 (8.3%)	7
Actinic keratosis	3/54 (5.6%)	3	6/84 (7.1%)	9
Rash maculo-papular	5/54 (9.3%)	6	6/84 (7.1%)	7
Dermatitis	0/54 (0%)	0	5/84 (6%)	6
Eczema	5/54 (9.3%)	7	5/84 (6%)	5
Vascular disorders
Hypertension	11/54 (20.4%)	29	8/84 (9.5%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.