Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Feb 2020 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2024-511653-22-00

EudraCT number

2019-000566-38

ClinicalTrials.gov

NCT03969004

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT).

Secondary objectives 6

1. To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT
2. To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT
3. To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT
4. To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT
5. To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT
6. To assess cemiplimab pharmacokinetics and immunogenicity in human serum

Conditions and MedDRA coding

Cutaneous Squamous Cell Carcinoma (CSCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
2. High risk CSCC
3. Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
4. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
5. Adequate hepatic, renal, and bone marrow function as defined in the protocol

Exclusion criteria 6

1. Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
2. Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
3. Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
4. Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
5. Has had prior systemic anti-cancer immunotherapy for CSCC
6. Note: Other protocol defined Inclusion/Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause.

Secondary endpoints 6

1. Overall survival (OS), defined as time from randomization to the date of death.
2. FFLRR defined as time from randomization to the date of first locoregional recurrence (LRR).
3. Freedom from distant recurrence (FFDR), defined as time from randomization to the date of first distant recurrence (DR). Patients who died without a preceding DR will be censored on the date of death.
4. Cumulative occurrence of second primary cutaneous squamous cell carcinoma tumor (SPTs) for each patient from randomization to occurrence of first primary endpoint event or end of study.
5. Safety, as measured by the incidence and severity of treatment-emergent adverse events (TEAE), deaths, and laboratory abnormalities.
6. Cemiplimab concentrations in serum and immunogenicity as measured in ADA in serum

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 16

Locations

8 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications