Advanced Cutaneous Squamous Cell Carcinoma
Conditions
Keywords
Metastatic CSCC, Unresectable locally advanced CSCC
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.
Interventions
DRUGcemiplimab
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Peak Concentration (Cmax) of Cemiplimab | Up to approximately 43 months | — |
Countries
Australia, Brazil, France, Germany, Greece, Italy, Spain, United States
Participant flow
Pre-assignment details
A total of 432 participants with advanced cutaneous squamous cell carcinoma (CSCC) (metastatic CSCC \[mCSCC\] or locally advanced CSCC \[laCSCC\]) were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W 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). | 59 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W Participants received cemiplimab 3 mg/kg IV Q2W during each 8-week treatment cycle, for up to 96 weeks (12 cycles). | 78 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W Participants received cemiplimab 350 mg IV every 3 weeks (Q3W) during each 9-week treatment cycle, for up to 54 weeks (6 cycles). | 56 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W Participants received cemiplimab 600 mg IV every 4 weeks (Q4W) during each 8-week treatment cycle, for up to 48 weeks (6 cycles). | 63 |
| Group 5 (Participants With mCSCC and laCSCC): Cemiplimab 438 mg SC + 350 mg IV Q3W Participants received a single 438 mg 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). | 9 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W Participants received cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 108 weeks (12 cycles). | 167 |
| Total | 432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 1 | 1 | 0 | 6 |
| Overall Study | Death | 7 | 5 | 5 | 7 | 0 | 23 |
| Overall Study | Disease progression | 21 | 19 | 20 | 18 | 4 | 55 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Non-compliance with study drug | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Not treated | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Other than specified | 1 | 6 | 0 | 3 | 1 | 0 |
| Overall Study | Participant decision | 1 | 4 | 2 | 2 | 1 | 6 |
| Overall Study | Physician Decision | 3 | 4 | 1 | 4 | 0 | 2 |
| Overall Study | Sponsor decision | 0 | 0 | 0 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 7 | 5 | 1 | 0 | 6 |
Baseline characteristics
| Characteristic | Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Group 5 (Participants With mCSCC and laCSCC): Cemiplimab 438 mg SC + 350 mg IV Q3W | Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized >= 65 to < 75 years | 23 Participants | 23 Participants | 20 Participants | 17 Participants | 4 Participants | 43 Participants | 130 Participants |
| Age, Customized < 65 years | 16 Participants | 19 Participants | 14 Participants | 16 Participants | 3 Participants | 30 Participants | 98 Participants |
| Age, Customized >= 75 years | 20 Participants | 36 Participants | 22 Participants | 30 Participants | 2 Participants | 94 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 75 Participants | 55 Participants | 62 Participants | 8 Participants | 147 Participants | 405 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 16 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 58 Participants | 75 Participants | 54 Participants | 61 Participants | 8 Participants | 164 Participants | 420 Participants |
| Sex: Female, Male Female | 5 Participants | 19 Participants | 8 Participants | 10 Participants | 4 Participants | 37 Participants | 83 Participants |
| Sex: Female, Male Male | 54 Participants | 59 Participants | 48 Participants | 53 Participants | 5 Participants | 130 Participants | 349 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 27 / 59 | 19 / 78 | 26 / 56 | 23 / 63 | 2 / 9 | 59 / 165 | 2 / 12 | 0 / 7 |
| other Total, other adverse events | 56 / 59 | 75 / 78 | 49 / 56 | 59 / 63 | 9 / 9 | 147 / 165 | 9 / 12 | 5 / 7 |
| serious Total, serious adverse events | 24 / 59 | 28 / 78 | 23 / 56 | 35 / 63 | 2 / 9 | 85 / 165 | 4 / 12 | 1 / 7 |
Outcome results
Primary
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
Population: The Full Analysis Set (FAS) included all enrolled participants. Only Groups 1, 2, 3, 4, and 6 were planned for this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Overall Response Rate (ORR) by Independent Central Review | 50.8 percentage of participants |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Overall Response Rate (ORR) by Independent Central Review | 44.9 percentage of participants |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Overall Response Rate (ORR) by Independent Central Review | 46.4 percentage of participants |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Overall Response Rate (ORR) by Independent Central Review | 61.9 percentage of participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Overall Response Rate (ORR) by Independent Central Review | 47.3 percentage of participants |
Secondary
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)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure and Number Analyzed is the number evaluable at each time point. Only Groups 1, 2, 3, and 4 were planned for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C3D1 | 11.26 score on a scale | Standard Deviation 19.267 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C12D1 | 8.33 score on a scale | Standard Deviation 22.388 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C8D1 | 4.60 score on a scale | Standard Deviation 21.08 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C11D1 | 10.33 score on a scale | Standard Deviation 28.186 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C10D1 | 12.04 score on a scale | Standard Deviation 20.844 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C9D1 | 6.09 score on a scale | Standard Deviation 18.938 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C4D1 | 6.25 score on a scale | Standard Deviation 25.069 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C7D1 | 6.51 score on a scale | Standard Deviation 17.676 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C6D1 | 5.11 score on a scale | Standard Deviation 17.437 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C5D1 | 4.17 score on a scale | Standard Deviation 22.316 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | Cycle 2 Day 1 (C2D1) | 0.00 score on a scale | Standard Deviation 21.464 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C5D1 | 8.33 score on a scale | Standard Deviation 21.246 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | Cycle 2 Day 1 (C2D1) | 5.56 score on a scale | Standard Deviation 18.895 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C3D1 | 5.30 score on a scale | Standard Deviation 21.717 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C8D1 | 10.10 score on a scale | Standard Deviation 21.425 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C10D1 | 13.77 score on a scale | Standard Deviation 26.064 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C12D1 | 12.75 score on a scale | Standard Deviation 24.494 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C4D1 | 8.76 score on a scale | Standard Deviation 19.585 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C6D1 | 5.68 score on a scale | Standard Deviation 28.118 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C7D1 | 9.17 score on a scale | Standard Deviation 22.393 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C9D1 | 6.61 score on a scale | Standard Deviation 26.199 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | 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 | C11D1 | 11.40 score on a scale | Standard Deviation 22.603 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C5D1 | 13.27 score on a scale | Standard Deviation 21.466 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C12D1 | 27.78 score on a scale | Standard Deviation 16.667 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C9D1 | 26.67 score on a scale | Standard Deviation 24.47 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C6D1 | 12.18 score on a scale | Standard Deviation 24.521 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C8D1 | 30.30 score on a scale | Standard Deviation 19.816 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | Cycle 2 Day 1 (C2D1) | 6.86 score on a scale | Standard Deviation 19.621 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C3D1 | 15.28 score on a scale | Standard Deviation 20.655 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C10D1 | 28.70 score on a scale | Standard Deviation 13.889 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C4D1 | 13.51 score on a scale | Standard Deviation 22.539 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C11D1 | 32.50 score on a scale | Standard Deviation 14.407 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | 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 | C7D1 | 22.22 score on a scale | Standard Deviation 23.659 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C10D1 | 5.83 score on a scale | Standard Deviation 22.923 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C5D1 | 5.79 score on a scale | Standard Deviation 18.774 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C4D1 | 4.39 score on a scale | Standard Deviation 15.099 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C12D1 | 2.78 score on a scale | Standard Deviation 26.021 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C6D1 | 0.25 score on a scale | Standard Deviation 21.599 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C3D1 | 3.88 score on a scale | Standard Deviation 15.68 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C9D1 | 7.69 score on a scale | Standard Deviation 20.543 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C8D1 | 5.00 score on a scale | Standard Deviation 25.158 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C11D1 | 14.81 score on a scale | Standard Deviation 19.444 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | C7D1 | 4.44 score on a scale | Standard Deviation 18.598 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | 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 | Cycle 2 Day 1 (C2D1) | 0.96 score on a scale | Standard Deviation 17.67 |
Secondary
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
Population: The FAS included all enrolled participants. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Complete Response (CR) Rate by Independent Central Review | 20.3 percentage of participants |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Complete Response (CR) Rate by Independent Central Review | 12.8 percentage of participants |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Complete Response (CR) Rate by Independent Central Review | 19.6 percentage of participants |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Complete Response (CR) Rate by Independent Central Review | 22.2 percentage of participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Complete Response (CR) Rate by Independent Central Review | 10.8 percentage of participants |
Secondary
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)
Population: The biomarker analysis set (BAS) included all participants in the FAS who had samples evaluable for PD-L1 assay. Here, 'Overall number of participants analyzed' signifies participants with confirmed CR or PR that are evaluable for this outcome measure and Number analyzed is the number of participants in each row category. Only Group 6 was planned for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 < 1% | 31.6 months |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 >= 1% | NA months |
Secondary
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)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants with confirmed CR or PR that are evaluable for this outcome measure. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | DOR by Investigator Assessment | NA months |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | DOR by Investigator Assessment | 41.9 months |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | DOR by Investigator Assessment | 44.2 months |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | DOR by Investigator Assessment | NA months |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | DOR by Investigator Assessment | NA months |
Secondary
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.
Time frame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants with confirmed CR or PR who were evaluable for this outcome measure. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Duration of Response (DOR) by Independent Central Review | NA months |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Duration of Response (DOR) by Independent Central Review | 41.9 months |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Duration of Response (DOR) by Independent Central Review | 41.3 months |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Duration of Response (DOR) by Independent Central Review | NA months |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Duration of Response (DOR) by Independent Central Review | 31.6 months |
Secondary
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)
Population: The Safety Analysis Set (SAF) included all enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 59 Participants |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 78 Participants |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 55 Participants |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 63 Participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 9 Participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | 163 Participants |
Secondary
Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies
Time frame: Up to approximately 43 months
Population: The Anti-drug Antibody (ADA) population for cemiplimab included all treated participants who had at least 1 postdose ADA result for cemiplimab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 1 Participants |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 0 Participants |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 0 Participants |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 0 Participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 0 Participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies | 5 Participants |
Secondary
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
Population: The biomarker analysis set (BAS) included all participants in the FAS who had samples evaluable for PD-L1 assay. Here, 'Overall number of participants analyzed' is the number of participants who are evaluable for this outcome measure and Number analyzed is the number of participants in each row category. Only Group 6 was planned for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 < 1% | 40.5 percentage of participants |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 >= 1% | 49.2 percentage of participants |
Secondary
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
Population: The FAS included all enrolled participants. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | ORR by Investigator Assessment | 50.8 percentage of participants |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | ORR by Investigator Assessment | 56.4 percentage of participants |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | ORR by Investigator Assessment | 55.4 percentage of participants |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | ORR by Investigator Assessment | 63.5 percentage of participants |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | ORR by Investigator Assessment | 52.7 percentage of participants |
Secondary
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)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants who received at least one dose of cemiplimab and were evaluable for this outcome measure. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Overall Survival (OS) | 57.7 months |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Overall Survival (OS) | NA months |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Overall Survival (OS) | 48.4 months |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Overall Survival (OS) | NA months |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Overall Survival (OS) | NA months |
Secondary
Peak Concentration (Cmax) of Cemiplimab
Time frame: Up to approximately 43 months
Population: The Pharmacokinetic (PK) analysis set included all participants who had received cemiplimab and had at least 1 qualified (non-missing) post-baseline measurement of cemiplimab concentration in serum. Here, Overall number of participants analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluable at each specified point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 108 milligram per liter (mg/L) | Standard Deviation 147 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 151 milligram per liter (mg/L) | Standard Deviation 83.7 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 84.1 milligram per liter (mg/L) | Standard Deviation 105 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 148 milligram per liter (mg/L) | Standard Deviation 76.6 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 132 milligram per liter (mg/L) | Standard Deviation 203 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 151 milligram per liter (mg/L) | Standard Deviation 46.2 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 174 milligram per liter (mg/L) | Standard Deviation 50.1 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 281 milligram per liter (mg/L) | Standard Deviation 235 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 52.9 milligram per liter (mg/L) | Standard Deviation 18.4 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 174 milligram per liter (mg/L) | Standard Deviation 62.2 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | After the First Dose | 96.3 milligram per liter (mg/L) | Standard Deviation 56.2 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Peak Concentration (Cmax) of Cemiplimab | At Steady State | 142 milligram per liter (mg/L) | Standard Deviation 78.3 |
Secondary
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)
Population: The biomarker analysis set (BAS) included all participants in the FAS who had samples evaluable for PD-L1 assay. Here, 'Overall number of participants analyzed' signifies participants who are evaluable for this outcome measure and Number analyzed is the number of participants in each row category. Only Group 6 was planned for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 < 1% | 10.7 months |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays | PD-L1 >= 1% | 16.6 months |
Secondary
PFS by Investigator Assessment
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)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants who received at least one dose of cemiplimab and were evaluable for this outcome measure. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | PFS by Investigator Assessment | 16.6 months |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | PFS by Investigator Assessment | 32.5 months |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | PFS by Investigator Assessment | 15.2 months |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | PFS by Investigator Assessment | 25.3 months |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | PFS by Investigator Assessment | 16.5 months |
Secondary
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)
Population: The FAS included all enrolled participants. Here, 'Overall number of participants analyzed' signifies participants who received at least one dose of cemiplimab and were evaluable for this outcome measure. Only Groups 1, 2, 3, 4, and 6 were planned for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Progression-Free Survival (PFS) by Independent Central Review | 18.4 months |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Progression-Free Survival (PFS) by Independent Central Review | 18.5 months |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Progression-Free Survival (PFS) by Independent Central Review | 21.7 months |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Progression-Free Survival (PFS) by Independent Central Review | 32.2 months |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Progression-Free Survival (PFS) by Independent Central Review | 16.6 months |
Secondary
Trough Concentration (Ctrough) of Cemiplimab
Time frame: Up to approximately 43 months
Population: The PK analysis set included all participants who had received cemiplimab and had at least 1 qualified (non-missing) post-baseline measurement of cemiplimab concentration in serum. Here, Overall number of participants analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluable at each specified point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 69.9 mg/L | Standard Deviation 19.3 |
| Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg IV Q2W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 21.5 mg/L | Standard Deviation 7.12 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 67.5 mg/L | Standard Deviation 29.8 |
| Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg IV Q2W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 26.3 mg/L | Standard Deviation 14.3 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 33.6 mg/L | Standard Deviation 32.1 |
| Group 3 (Participants With mCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 62.7 mg/L | Standard Deviation 28.3 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 62.5 mg/L | Standard Deviation 24.1 |
| Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg IV Q4W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 32.1 mg/L | Standard Deviation 10.4 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 34.1 mg/L | Standard Deviation 14.1 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 65.9 mg/L | Standard Deviation 22.9 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | At Steady State | 53.3 mg/L | Standard Deviation 20.1 |
| Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg IV Q3W | Trough Concentration (Ctrough) of Cemiplimab | After the First Dose | 23.0 mg/L | Standard Deviation 10.9 |