Cutaneous Squamous Cell Carcinoma
Conditions
Keywords
CSCC, Stage II, Stage III, Stage IV, CSCC of Head/neck, CSCC of Extremity, CSCC of Trunk
Brief summary
The primary objective of the study is to evaluate the efficacy of neoadjuvant cemiplimab as measured by Pathologic complete response (pCR) rate per independent central pathology review. The secondary objectives of the study are: * To evaluate the efficacy of neoadjuvant cemiplimab on measures of disease response, including: * Major pathologic response (mPR) rate per independent central pathology review * pCR rate and mPR rate per local pathology review * ORR prior to surgery, according to local assessment using RECIST 1.1 * To evaluate the efficacy of neoadjuvant cemiplimab on event free survival (EFS), disease free survival (DFS), and overall survival (OS) * To evaluate the safety profile of neoadjuvant cemiplimab * To assess change in surgical plan (ablative and reconstructive procedures) from the screening period to definitive surgery, both according to investigator review and independent surgical expert review * To assess change in post-surgical management plan (radiation, chemoradiation, or observation) from the screening period to post-surgery pathology review, both according to investigator review and independent surgical expert review
Interventions
DRUGCemiplimab
Intravenous (IV) infusion every 3 weeks (Q3W)
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Stage II to IV (M0) CSCC, for which surgery would be recommended in routine clinical practice. For stage II patients, lesion must be ≥3 cm at the longest diameter. * At least 1 lesion that is measurable by RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ, bone marrow function, and hepatic function as defined in the protocol Key
Exclusion criteria
* Solid malignancy within 5 years of the projected enrollment date, or hematologic malignancy (including chronic lymphocytic leukemia \[CLL\]) at any time * Distant metastatic disease (M1), visceral and/or distant nodal * Prior radiation therapy for CSCC * Patients with a condition requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 14 days of the first dose of study drug. * Patients with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date. * History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. * Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus (HBV or HCV) infection; or diagnosis of immunodeficiency * Active tuberculosis NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Pathologic Complete Response (pCR) as Assessed by Independent Central Pathology Review | Up to 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Pathologic Complete Response (pCR) as Assessed by Local Pathology Review | Up to 12 weeks |
| Number of Participants With Major Pathologic Response (mPR) as Assessed by Local Pathology Review | Up to 12 Weeks |
| Percentage of Participants With Objective Response Rate (ORR) Prior to Surgery, According to Investigator Assessment Using RECIST 1.1 | Up to 12 Weeks |
| Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab | Up to 12 Weeks |
| Number of Participants With Planned and Actual Post-Surgical Management | Up to 14 Weeks |
| Event Free Survival (EFS) | Up to 50 Months |
| Number of Participants With Major Pathologic Response (mPR) as Assessed by Independent Central Pathology Review | Up to 12 Weeks |
| Overall Survival (OS) | Up to 50 Months |
| Incidence of Adverse Events (AEs) | Up to 52 Months |
| Incidence of Serious Adverse Events (SAEs) | Up to 52 Months |
| Incidence of Deaths | Up to 52 Months |
| Incidence of Laboratory Abnormalities | Up to 52 Months |
| Disease Free Survival (DFS) | Up to 47 Months |
Countries
Australia, Germany, United States
Participant flow
Pre-assignment details
As of the data cutoff (01 Dec 2021), 101 participants were screened for study eligibility. 79 participants were randomized and received at least 1 dose of cemiplimab.
Participants by arm
| Arm | Count |
|---|---|
| Cemiplimab 350mg Q3W Participants received cemiplimab, administered at a dose of 350mg every 3 weeks for up to 4 doses | 79 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Decision by the Investigator | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Study Ongoing | 68 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Cemiplimab 350mg Q3W |
|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 11.3 |
| Age, Customized 17 years and under | 0 Participants |
| Age, Customized 18 to 64 years | 18 Participants |
| Age, Customized 65 to 84 years | 54 Participants |
| Age, Customized 85 years and over | 7 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 74 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized Unknown / Not Reported | 8 Participants |
| Race/Ethnicity, Customized Unknown/Not Reported | 5 Participants |
| Race/Ethnicity, Customized White | 69 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 79 |
| other Total, other adverse events | 60 / 79 |
| serious Total, serious adverse events | 15 / 79 |
Outcome results
Primary
Number of Participants With Pathologic Complete Response (pCR) as Assessed by Independent Central Pathology Review
Time frame: Up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Pathologic Complete Response (pCR) as Assessed by Independent Central Pathology Review | 40 Participants |
Secondary
Disease Free Survival (DFS)
Time frame: Up to 47 Months
Secondary
Event Free Survival (EFS)
Time frame: Up to 50 Months
Secondary
Incidence of Adverse Events (AEs)
Time frame: Up to 52 Months
Secondary
Incidence of Deaths
Time frame: Up to 52 Months
Secondary
Incidence of Laboratory Abnormalities
Time frame: Up to 52 Months
Secondary
Incidence of Serious Adverse Events (SAEs)
Time frame: Up to 52 Months
Secondary
Number of Participants With Major Pathologic Response (mPR) as Assessed by Independent Central Pathology Review
Time frame: Up to 12 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Major Pathologic Response (mPR) as Assessed by Independent Central Pathology Review | 10 Participants |
Secondary
Number of Participants With Major Pathologic Response (mPR) as Assessed by Local Pathology Review
Time frame: Up to 12 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Major Pathologic Response (mPR) as Assessed by Local Pathology Review | 10 Participants |
Secondary
Number of Participants With Pathologic Complete Response (pCR) as Assessed by Local Pathology Review
Time frame: Up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Pathologic Complete Response (pCR) as Assessed by Local Pathology Review | 42 Participants |
Secondary
Number of Participants With Planned and Actual Post-Surgical Management
Time frame: Up to 14 Weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Post-Surgical Management | Planned radiation therapy after surgery | 47 Participants |
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Post-Surgical Management | Actual radiation therapy after surgery | 17 Participants |
Secondary
Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab
Time frame: Up to 12 Weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab | Participants with Planned Mohs Surgery | 2 Participants |
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab | Participants with Actual Mohs Surgery | 2 Participants |
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab | Participants with Planned Non-Mohs Surgery | 77 Participants |
| Cemiplimab 350mg Q3W | Number of Participants With Planned and Actual Surgery After Neoadjuvant Cemiplimab | Participants with Actual Non-Mohs Surgery | 68 Participants |
Secondary
Overall Survival (OS)
Time frame: Up to 50 Months
Secondary
Percentage of Participants With Objective Response Rate (ORR) Prior to Surgery, According to Investigator Assessment Using RECIST 1.1
Time frame: Up to 12 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cemiplimab 350mg Q3W | Percentage of Participants With Objective Response Rate (ORR) Prior to Surgery, According to Investigator Assessment Using RECIST 1.1 | 68.4 Percentage of Participants |