Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
- Registration Number
- NCT02760498
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The goals of this study are to evaluate the clinical benefit and safety of cemiplimab in participants with metastatic (nodal or distant) Cutaneous Squamous Cell Carcinoma (CSCC), or unresectable locally advanced CSCC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 432
- At least 1 measurable lesion
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate bone marrow function
- Adequate renal function
- Adequate hepatic function
- Archived or newly obtained tumor material
- Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6)
- Surgical or radiological treatment of lesions contraindicated
Key
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events
- Prior treatment with an agent that blocks the PD-1/PD-L1pathway
- Prior treatment with a BRAF inhibitor
- Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
- Untreated brain metastasis(es) that may be considered active
- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
- Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus
- History of non-infectious pneumonitis within the last 5 years
- Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
- Known allergy to doxycycline or tetracycline
- Patients with a history of solid organ transplant
- Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg Q2W cemiplimab Participants received cemiplimab 3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks (Q2W) during each 8-week treatment cycle, for up to 96 weeks (12 cycles). Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg Q2W cemiplimab Participants received cemiplimab 3 mg/kg IV Q2W during each 8-week treatment cycle, for up to 96 weeks (12 cycles). Group 3 (Participants With mCSCC): Cemiplimab 350 mg Q3W cemiplimab Participants received cemiplimab 350 mg IV every 3 weeks (Q3W) during each 9-week treatment cycle, for up to 54 weeks (6 cycles). Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg Q4W cemiplimab Participants received cemiplimab 600 mg IV every 4 weeks (Q4W) during each 8-week treatment cycle, for up to 48 weeks (6 cycles). Group 5 (Participants With mCSCC and laCSCC): Cemiplimab SC + 350 mg Q3W cemiplimab Participants received a single subcutaneous (SC) dose of cemiplimab followed by cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 54 weeks (6 cycles). Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg Q3W cemiplimab Participants received cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 108 weeks (12 cycles).
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by Independent Central Review Up to 108 weeks ORR was defined as percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). For participants with metastatic disease, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) \<1 (centimeter (cm). -PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
- Secondary Outcome Measures
Name Time Method ORR by Investigator Assessment Up to 108 weeks ORR was defined as percentage of participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -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. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
Duration of Response (DOR) by Independent Central Review Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria were first met for CR/PR, whichever was recorded first, until the first date of recurrent or Progressive Disease (PD) or death due to any cause in participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
DOR by Investigator Assessment Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria were first met for CR/PR, as defined in Outcome Measure 1, whichever was recorded first, until the first date of recurrent or Progressive Disease (PD) or death due to any cause in participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (World Health Organization (WHO) criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Progression-Free Survival (PFS) by Independent Central Review Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from start of treatment until the first date of recurrent or PD, or death due to any cause. For participants with metastatic disease, RECIST v1.1 was used to determine PD. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
PFS by Investigator Assessment Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from start of treatment until the first date of recurrent or PD, or death due to any cause. For participants with metastatic disease, RECIST v1.1 was used to determine PD. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Overall Survival (OS) Up to approximately 65 months (treatment period + follow-up including survival follow-up) OS was measured from start of treatment until death due to any cause.
Complete Response (CR) Rate by Independent Central Review Up to 108 weeks CR rate was defined as percentage of participants with BOR of CR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -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. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Score Baseline, Up to Cycle 12 Day 1 (Week 89) EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria are first met for CR/PR, as defined in Outcome Measure 13, whichever was recorded first, until the first date of recurrent or PD or death due to any cause in participants with BOR of CR or PR. Expression level of PD-L1 was assessed in tumor biopsy samples by IHC. -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Number of Participants With Any Treatment Emergent Adverse Event (TEAE) Up to 108 weeks plus 105 days (5 half-lives) An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-emergent adverse events (TEAEs) are defined as those not present at baseline or represent the exacerbation of a condition present at baseline during the on-treatment period or follow-up period. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Peak Concentration (Cmax) of Cemiplimab Up to approximately 43 months Trough Concentration (Ctrough) of Cemiplimab Up to approximately 43 months Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies Up to approximately 43 months ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to 108 weeks ORR was defined as percentage of participants with BOR of CR or PR. Expression level of PD-L1 was assessed in tumor biopsy samples by immunohistochemistry (IHC). -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from time of enrollment until the first date of recurrent or progressive disease, or death due to any cause. Expression level of PD-L1 was assessed in tumor biopsy samples. -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Trial Locations
- Locations (78)
University of Arizona Cancer Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
City of Hope Hospital
🇺🇸Duarte, California, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Redwood City, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
University of Colorado, Denver
🇺🇸Aurora, Colorado, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Scroll for more (68 remaining)University of Arizona Cancer Center🇺🇸Phoenix, Arizona, United States