Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Regeneron Pharmaceuticals432 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

432

Conditions

Advanced Cutaneous Squamous Cell Carcinoma

Interventions

cemiplimabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (78)

Outcomes

Primary Outcomes

Overall Response Rate (ORR) by Independent Central Review

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.

Time frame: Up to 108 weeks

Secondary Outcomes

ORR by Investigator Assessment

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.

Time frame: Up to 108 weeks

Duration of Response (DOR) by Independent Central Review

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

...and 68 more locations

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

DOR by Investigator Assessment

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.

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

Progression-Free Survival (PFS) by Independent Central Review

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.

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

PFS by Investigator Assessment

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

Overall Survival (OS)

OS was measured from start of treatment until death due to any cause.

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

Complete Response (CR) Rate by Independent Central Review

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.

Time frame: Up to 108 weeks

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

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.

Time frame: Baseline, Up to Cycle 12 Day 1 (Week 89)

Number of Participants With Any Treatment Emergent Adverse Event (TEAE)

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.

Time frame: Up to 108 weeks plus 105 days (5 half-lives)

Peak Concentration (Cmax) of Cemiplimab

Time frame: Up to approximately 43 months

Trough Concentration (Ctrough) of Cemiplimab

Time frame: Up to approximately 43 months

Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies

Time frame: Up to approximately 43 months

ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays

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.

Time frame: Up to 108 weeks

DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays

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.

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)

PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays

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.

Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)