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

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

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

Study Overview

• Status: Completed
• Conditions: Carcinoma, Basal Cell
• Intervention / Treatment: Drug: cemiplimab

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rates (ORR) as Assessed by Independent Central Review (ICR)	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.	Up to 1422 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) Per ICR	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.	Up to 40 months
Duration of Response (DOR) Per Investigator Assessment	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.	Up to 40 months
Progression Free Survival (PFS) Determined by ICR	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.	Up to 40 months
Progression Free Survival (PFS) Determined by Investigator Assessment	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.	Up to 40 months
Overall Survival (OS)	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.	Up to 40 months
Percentage of Participants With Complete Response (CR) Rate Assessed by ICR	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).	Up to 1422 days
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)	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.	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])
Change From Baseline of Patient-reported Outcomes in Skindex-16 Questionnaire	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.	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])
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	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.	Up to 1422 days
Serum Concentration at End of Infusion (Cmax) of Cemiplimab	Cmax of cemiplimab was reported.	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)
Serum Concentration at Pre-infusion (Ctrough) of Cemiplimab	Ctrough of cemiplimab was reported.	At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks)
Number of Participants With Anti-Drug Antibody (ADA) Status	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.	Cycle 1: Days 1 and 43; Cycles 3 and 5: Day 1 (Each cycle of 9 weeks)

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Stratigos AJ, Sekulic A, Peris K, Bechter O, Prey S, Kaatz M, Lewis KD, Basset-Seguin N, Chang ALS, Dalle S, Orland AF, Licitra L, Robert C, Ulrich C, Hauschild A, Migden MR, Dummer R, Li S, Yoo SY, Mohan K, Coates E, Jankovic V, Fiaschi N, Okoye E, Bassukas ID, Loquai C, De Giorgi V, Eroglu Z, Gutzmer R, Ulrich J, Puig S, Seebach F, Thurston G, Weinreich DM, Yancopoulos GD, Lowy I, Bowler T, Fury MG. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):848-857. doi: 10.1016/S1470-2045(21)00126-1. Epub 2021 May 14.
• Li R, Lee G, Huang M, El-Sherief A. Rare basal cell metastasis of a basal-squamous skin collision tumour to the lung and axillary lymph node. BMJ Case Rep. 2019 Oct 3;12(10):e231487. doi: 10.1136/bcr-2019-231487.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R2810-ONC-1620; 2016-003122-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No