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

Carcinoma, Basal Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03132636
• Other study ID #: R2810-ONC-1620
• Secondary ID: 2016-003122-16
• Status: Completed
• Phase: Phase 2
• Start date: June 29, 2017
• Est. completion date: April 27, 2023

Study information

• Verified date: April 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: April 27, 2023
• Est. primary completion date: May 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Basal Cell

Intervention

Drug:
• cemiplimab
Regimen as per protocol

Locations

Country	Name	City	State
Austria	LKH - Universitaetsklinikum Graz	Graz	Steiermark
Austria	Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Dermatologie, Venerologie und Allergologie	Innsbruck
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program, London Hsc	Toronto	Ontario
Canada	Odette Cancer Center-Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
France	Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Saint-André - Hôpital Saint-André	Bordeaux
France	Hopital Ambroise Pare	Boulogne Billancourt
France	CHU de Dijon - Hopital du Bocage	Dijon	Cedex
France	Centre Hospitalier Universitaire de Grenoble	La Tronche
France	Hopital Huriez - CHRU de Lille	Lille Cedex
France	Centre Leon-Berard (CLB)	Lyon
France	CHU Hotel Dieu	Nantes
France	Hopital Saint Louis	Paris	Europe
France	Centre Hospitalier Lyon-Sud -Hospices Civils de Lyon Groupement Hospitalier Sud	Pierre Benite Cedex	Paris
France	Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle	Rouen cedex
France	Institut Claudius Regaud	Toulouse Cedex
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Hauttumorcentrum der Charite (HTCC)-Charite Universitatsmedizin Berlin	Berlin
Germany	Elbekliniken Buxtehude	Buxtehude
Germany	University Hospital Dresden	Dresden
Germany	Universitaetsklinik Essen	Essen
Germany	University Hospital Frankfurt	Frankfurt	Hessen/Germany
Germany	SRH Wald-Kliniken Gera GmbH	Gera
Germany	Hannover Medical School	Hannover
Germany	NCT Dermatoonkologie	Heidelberg
Germany	University of Kiel	Kiel
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Klinik Fur Dermatologie Und Allergollogie	Quedlinburg
Germany	University Hospital Tubingen	Tübingen
Greece	Andreas Sygros Hosptial-University of Athen	Athens
Greece	National and Kapodistrian University of Athens - School of Health Sciences	Athens
Greece	National and Kapodistrian University of Athens - School of Health Sciences - Faculty of Medicine	Athens
Greece	University General Hospital of Ioannina - Dermatology and Venereology Department	Ioánnina
Italy	Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna	Bologna	Bo
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia	Brescia	Province Of Brescia
Italy	U.O.Dermatologia Azienda Sanitaria Firenze Universita' Firenze	Firenze
Italy	University L'Aquila	L'Aquila
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	U.O.S.C Di Oncologia Medica E Terapie Innovative	Napoli
Italy	Catholic University of the S.Heart	Roma
Spain	Catalan Institute of Oncology Badalona	Badalona
Spain	Hospital Clinic I Provincialde Barcelona	Barcelona
Spain	Hospital Universitario de Torrejon	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Switzerland	University Hospital Zurich Usz	Zürich
United States	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Clinical Research Center of the Carolinas	Charleston	South Carolina
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	University of Colorado Hospital, Anschutz Outpatient Pavilion	Denver	Colorado
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Mount Sinai Comprehensive Cancer Center	Miami	Florida
United States	Atlantic Health System / Morristown Medical Center	Morristown	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	New York University School Of Medicine, Kaplan Comprehensive Cancer Center	New York	New York
United States	Mayo Clinic Arizona - Mayo Clinic Hospital	Phoenix	Arizona
United States	The University of Arizona Cancer Centre at Dignity Health	Phoenix	Arizona
United States	Stanford Medicine Outpatient Center - Stanford Dermatology Clinic-Stanford University School of Medicine	Redwood City	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Helen Dillion Family Cancer Care Center	San Francisco	California
United States	Overlook Medical Center	Summit	New Jersey
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Greece,  Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (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 (approximately 46 months)
Secondary	Objective Response Rate (ORR) Per Investigator Assessment	ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 per Investigator 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 (approximately 46 months)
Secondary	Duration of Response (DOR) as Assessed by 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 48 months
Secondary	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 48 months
Secondary	Complete Response (CR) Rate as Assessed by ICR	CR rate 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). CR rate 95% confidence interval determined by Clopper-Pearson exact confidence interval.	Up to 48 months
Secondary	Complete Response (CR) Rate Per Investigator Assessment	CR rate 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). CR rate 95% confidence interval determined by Clopper-Pearson exact confidence interval.	Up to 48 months
Secondary	Progression Free Survival (PFS) as Assessed 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 60 months
Secondary	Progression Free Survival (PFS) Per 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 60 months
Secondary	Overall Survival (OS)	OS was measured as time from the start of treatment until death due to any cause. Participants who did not die were censored at the last date that participant was documented to be alive. OS was calculated based on Kaplan-Meier estimate.	Up to 60 months
Secondary	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])
Secondary	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])
Secondary	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 (approximately 46 months)
Secondary	Serum Concentration at Pre-infusion (Ctrough)	Ctrough of cemiplimab reported.	At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks)
Secondary	Serum Concentration at End of Infusion (Cmax)	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)
Secondary	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)