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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

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ClinicalTrials.gov Identifier: NCT03132636
Recruitment Status : Active, not recruiting
First Posted : April 28, 2017
Results First Posted : July 26, 2022
Last Update Posted : July 26, 2022
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 24, 2017
First Posted Date  ICMJE April 28, 2017
Results First Submitted Date  ICMJE May 17, 2022
Results First Posted Date  ICMJE July 26, 2022
Last Update Posted Date July 26, 2022
Actual Study Start Date  ICMJE June 29, 2017
Actual Primary Completion Date May 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2022)
Objective Response Rates (ORR) as Assessed by Independent Central Review (ICR) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Overall Response Rate (ORR) for metastatic Basal Cell Carcinoma (BCC) [ Time Frame: Baseline to 93 weeks ]
    ORR for metastatic BCC measured by RECIST version 1.1
  • ORR for unresectable locally advanced BCC [ Time Frame: Baseline to 93 weeks ]
    ORR for unresectable locally advanced BCC measured by Composite Response Criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2022)
  • Duration of Response (DOR) Per ICR [ Time Frame: 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.
  • Duration of Response (DOR) Per Investigator Assessment [ Time Frame: 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.
  • Progression Free Survival (PFS) Determined by ICR [ Time Frame: 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.
  • Progression Free Survival (PFS) Determined by Investigator Assessment [ Time Frame: 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.
  • Overall Survival (OS) [ Time Frame: 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.
  • Percentage of Participants With Complete Response (CR) Rate Assessed by ICR [ Time Frame: 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).
  • 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) [ 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]) ]
    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 [ 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]) ]
    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 [ Time Frame: 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.
  • Serum Concentration at End of Infusion (Cmax) of Cemiplimab [ 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) ]
    Cmax of cemiplimab was reported.
  • Serum Concentration at Pre-infusion (Ctrough) of Cemiplimab [ Time Frame: At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks) ]
    Ctrough of cemiplimab was reported.
  • Number of Participants With Anti-Drug Antibody (ADA) Status [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Duration of Response (DOR) [ Time Frame: Time from the first observed confirmed response to disease progression or death, up to approximately 119 weeks ]
    DOR assessed by time from the first observed confirmed response (CR or PR) to disease progression or death, up to approximately 119 weeks (from first response assessment until end of post-treatment follow up)
  • Complete Response (CR) Rate [ Time Frame: From date of treatment until best overall response of CR after starting REGN2810, up to approximately 119 weeks ]
    CR rate (per central review) assessed from date of treatment until best overall response of CR after starting REGN2810 treatment, up to approximately 119 weeks (from first response assessment until end of post-treatment follow up).
  • Progression Free Survival (PFS) [ Time Frame: From date of treatment until date of death up to approximately 119 weeks ]
    PFS assessed from date of treatment until date of death, up to approximately 119 weeks
  • Overall Survival (OS) [ Time Frame: From date of treatment until date of death, up to approximately 119 weeks ]
    OS assessed from date of treatment until date of death, up to approximately 119 weeks
  • Change in scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
    Change in scores of patient-reported outcomes in EORTC QLQ-C30 assessed from date of treatment until date of first documented progression or date of death, up to approximately 93 weeks
  • Change in scores of patient-reported outcomes in Skindex-16 [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
    From date of treatment until date of first documented progression or date of death, assessed up to approximately 93 weeks
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Basal Cell
Intervention  ICMJE Drug: cemiplimab
Regimen as per protocol
Other Names:
  • REGN2810
  • Libtayo
Study Arms  ICMJE
  • Experimental: Group 1- metastatic BCC
    Administration of cemiplimab in accordance with protocol dosing regimen
    Intervention: Drug: cemiplimab
  • Experimental: Group 2 - unresectable locally advanced BCC
    Administration of cemiplimab in accordance with protocol dosing regimen
    Intervention: Drug: cemiplimab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 17, 2022)
138
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2017)
137
Estimated Study Completion Date  ICMJE May 29, 2023
Actual Primary Completion Date May 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   France,   Germany,   Greece,   Italy,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03132636
Other Study ID Numbers  ICMJE R2810-ONC-1620
2016-003122-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Regeneron Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Regeneron Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP