Ignite Creation Date:
2025-12-25 @ 2:50 AM
Ignite Modification Date:
2025-12-26 @ 1:32 AM
Study NCT ID:
NCT04632433
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-03-13
First Post:
2020-11-06
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in Cutaneaous Squamous Cell Carcinoma
Sponsor:
Fondazione Melanoma Onlus
Organization:
Study Overview
Official Title:
A Phase II, Single Arm Study Investigating Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in High Risk, Surgically Resectable, Stage III Cutaneaous Squamous Cell Carcinoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Neoadjuvant plus adjuvant treatment with immunotherapy may have an anti-tumor activity and reduce the risk of relapse in patients with high risk surgically resectable stage III cutaneous squamous cell carcinoma.
Detailed Description:
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in US. It is associated with a surgical cure rate \>95% in early stage disease but a small percentage of patients develop unresectable locally advanced or metastatic CSCC. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Conventional cytotoxic chemotherapy can induce tumor responses but is often poorly tolerated, specially among older patients with CSCC. CSCC has higher mutation burden than any tumor type and immunosuppression is a known risk factor. Furthermore, PD-L1 expression has been associated with high risk disease1 suggesting that CSCC may be responsive to PD-1 checkpoint blockade.
Cemiplimab is a human anti-PD-1 monoclonal antibody, under study for patients with unresectable locally advanced and/or regionally or metastatic CSCC. It has been studied in a phase I dose escalation, where a durable radiologic complete response was achieved in CSCC patients.2-3 In this study, the partial response was 25% in locally advanced and 60% in metastatic CSCC,stable disease was 31.3% in locally advanced and 10% in metastatic CSCC, progressive disease was 25% in locally advanced and 20% in metastatic CSCC with an overall response rate of 46.2% and a disease control rate of 69.2%. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC. The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR).
Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.
Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.
Cemiplimab therefore produced rapid, deep and durable tumor reductions in target lesions.
Cemiplimab appears to be active regardless PD-L1 expressione in the tumor and no apparent association between PD-L1 IHC results and objective responses was determined. Cemiplimab was generally well tolerated in CSCC, and most commonly associated with fatigue (23.1% prevalence), arthralgia, rash maculopapular, diarrhea, nausea, hypothyroidism (7.7%) of any grade.
The advantage of neoadjuvant trials is the availability of blood and tumor tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumor microenvironment.
Based on the available results to date, the investigators aim to conduct a phase II single arm trial to define the role of neoadjuvant plus adjuvant immunotherapy in patients with stage III CSCC. This approach has the potential to define whether neoadjuvant treatment with cemiplimab has antitumor activity and whether it reduces the risk of relapse after surgery.
Cemiplimab is a human anti-PD-1 monoclonal antibody, under study for patients with unresectable locally advanced and/or regionally or metastatic CSCC. It has been studied in a phase I dose escalation, where a durable radiologic complete response was achieved in CSCC patients.2-3 In this study, the partial response was 25% in locally advanced and 60% in metastatic CSCC,stable disease was 31.3% in locally advanced and 10% in metastatic CSCC, progressive disease was 25% in locally advanced and 20% in metastatic CSCC with an overall response rate of 46.2% and a disease control rate of 69.2%. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC. The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR).
Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.
Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.
Cemiplimab therefore produced rapid, deep and durable tumor reductions in target lesions.
Cemiplimab appears to be active regardless PD-L1 expressione in the tumor and no apparent association between PD-L1 IHC results and objective responses was determined. Cemiplimab was generally well tolerated in CSCC, and most commonly associated with fatigue (23.1% prevalence), arthralgia, rash maculopapular, diarrhea, nausea, hypothyroidism (7.7%) of any grade.
The advantage of neoadjuvant trials is the availability of blood and tumor tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumor microenvironment.
Based on the available results to date, the investigators aim to conduct a phase II single arm trial to define the role of neoadjuvant plus adjuvant immunotherapy in patients with stage III CSCC. This approach has the potential to define whether neoadjuvant treatment with cemiplimab has antitumor activity and whether it reduces the risk of relapse after surgery.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: