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
- Registration Number
- NCT03132636
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 138
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1- metastatic BCC cemiplimab Administration of cemiplimab in accordance with protocol dosing regimen Group 2 - unresectable locally advanced BCC cemiplimab Administration of cemiplimab in accordance with protocol dosing regimen
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed by Independent Central Review (ICR) Up to 1422 days (approximately 46 months) 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
Name Time Method Objective Response Rate (ORR) Per Investigator Assessment Up to 1422 days (approximately 46 months) 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.
Duration of Response (DOR) as Assessed by ICR Up to 48 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.
Duration of Response (DOR) Per Investigator Assessment Up to 48 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.
Complete Response (CR) Rate as Assessed by ICR Up to 48 months 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.
Complete Response (CR) Rate Per Investigator Assessment Up to 48 months 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.
Progression Free Survival (PFS) as Assessed by ICR Up to 60 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.
Progression Free Survival (PFS) Per Investigator Assessment Up to 60 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.
Overall Survival (OS) Up to 60 months 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.
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.
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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Up to 1422 days (approximately 46 months) 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.
Serum Concentration at Pre-infusion (Ctrough) At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks) Ctrough of cemiplimab reported.
Serum Concentration at End of Infusion (Cmax) 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.
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.
Trial Locations
- Locations (71)
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Overlook Medical Center
🇺🇸Summit, New Jersey, United States
Hopital Huriez - CHRU de Lille
🇫🇷Lille Cedex, France
Atlantic Health System / Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
LKH - Universitaetsklinikum Graz
🇦🇹Graz, Steiermark, Austria
Hopital Ambroise Pare
🇫🇷Boulogne Billancourt, France
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Centre Leon-Berard (CLB)
🇫🇷Lyon, France
CHU de Dijon - Hopital du Bocage
🇫🇷Dijon, Cedex, France
University General Hospital of Ioannina - Dermatology and Venereology Department
🇬🇷Ioánnina, Greece
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
London Regional Cancer Program, London Hsc
🇨🇦Toronto, Ontario, Canada
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Mayo Clinic Arizona - Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
UCSF Helen Dillion Family Cancer Care Center
🇺🇸San Francisco, California, United States
The University of Arizona Cancer Centre at Dignity Health
🇺🇸Phoenix, Arizona, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford Medicine Outpatient Center - Stanford Dermatology Clinic-Stanford University School of Medicine
🇺🇸Redwood City, California, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Colorado Hospital, Anschutz Outpatient Pavilion
🇺🇸Denver, Colorado, United States
H Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
New York University School Of Medicine, Kaplan Comprehensive Cancer Center
🇺🇸New York, New York, United States
James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Clinical Research Center of the Carolinas
🇺🇸Charleston, South Carolina, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Dermatologie, Venerologie und Allergologie
🇦🇹Innsbruck, Austria
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
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 Bordeaux - Groupe Hospitalier Saint-André - Hôpital Saint-André
🇫🇷Bordeaux, France
CHU Hotel Dieu
🇫🇷Nantes, France
Centre Hospitalier Universitaire de Grenoble
🇫🇷La Tronche, France
Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
🇫🇷Rouen cedex, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Hauttumorcentrum der Charite (HTCC)-Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Institut Claudius Regaud
🇫🇷Toulouse Cedex, France
University Hospital Frankfurt
🇩🇪Frankfurt, Hessen/Germany, Germany
Elbekliniken Buxtehude
🇩🇪Buxtehude, Germany
University Hospital Dresden
🇩🇪Dresden, 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
National and Kapodistrian University of Athens - School of Health Sciences - Faculty of Medicine
🇬🇷Athens, Greece
National and Kapodistrian University of Athens - School of Health Sciences
🇬🇷Athens, Greece
Klinik Fur Dermatologie Und Allergollogie
🇩🇪Quedlinburg, Germany
Andreas Sygros Hosptial-University of Athen
🇬🇷Athens, Greece
University L'Aquila
🇮🇹L'Aquila, Italy
Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna
🇮🇹Bologna, Bo, Italy
U.O.Dermatologia Azienda Sanitaria Firenze Universita' Firenze
🇮🇹Firenze, Italy
Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
🇮🇹Brescia, Province Of Brescia, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Catholic University of the S.Heart
🇮🇹Roma, Italy
Catalan Institute of Oncology Badalona
🇪🇸Badalona, Spain
U.O.S.C Di Oncologia Medica E Terapie Innovative
🇮🇹Napoli, Italy
Hospital Clinic I Provincialde Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de Torrejon
🇪🇸Madrid, Spain
University Hospital Zurich Usz
🇨🇭Zürich, Switzerland
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Odette Cancer Center-Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Universitaetsklinik Essen
🇩🇪Essen, Germany
University Hospital Tubingen
🇩🇪Tübingen, Germany
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium