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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Carcinoma, Basal Cell

Intervention / Treatment
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* Drug: cemiplimab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1- metastatic BCC<br>Administration of cemiplimab in accordance with protocol dosing regimen | Drug: cemiplimab<br>* Regimen as per protocol<br>* Other names: Libtayo;|
| Experimental: Group 2 - unresectable locally advanced BCC<br>Administration of cemiplimab in accordance with protocol dosing regimen | Drug: cemiplimab<br>* Regimen as per protocol<br>* Other names: Libtayo;|

What is the study measuring?
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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) |