Intralesional Cemiplimab for Patients With Cutaneous Squamous Cell Carcinoma or Basal Cell Carcinoma

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03889912

Collaborator

Sanofi (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective is to characterize the safety and tolerability of cemiplimab injected intralesionally in patients with Cutaneous Squamous Cell Carcinoma (CSCC) or Basal Cell Carcinoma (BCC)

The secondary objectives of this study are:

To describe the objective response rate (ORR) in CSCC or BCC index lesions following intralesional injections of cemiplimab in patients with CSCC or BCC, according to modified World Health Organization (WHO) criteria
To describe the pathologic complete response (CR) rate in CSCC or BCC index lesions following intralesional injections of cemiplimab in patients with CSCC or BCC
To describe the major pathologic response rate in CSCC or BCC index lesions following intralesional injections of cemiplimab in patients with CSCC or BCC
To evaluate systemic exposure of cemiplimab following intralesional injections of cemiplimab in patients with CSCC or BCC
To assess the immunogenicity of cemiplimab in patients with CSCC or BCC
To establish a recommended dose of intralesional cemiplimab for further study in patients with CSCC or BCC

Condition or Disease	Intervention/Treatment	Phase
Cutaneous Squamous Cell Carcinoma Basal Cell Carcinoma	Drug: Cemiplimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

61 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Cohorts A and B will enroll sequentially (not randomized). Cohort C for BCC will enroll in parallel with, and independently of, Cohorts A and B for CSCC patientsCohorts A and B will enroll sequentially (not randomized). Cohort C for BCC will enroll in parallel with, and independently of, Cohorts A and B for CSCC patients

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Pre-Operative Cemiplimab (REGN2810), Administered Intralesionally, for Patients With Cutaneous Squamous Cell Carcinoma (CSCC) or Basal Cell Carcinoma (BCC)

Actual Study Start Date :

Apr 11, 2019

Anticipated Primary Completion Date :

Oct 26, 2023

Anticipated Study Completion Date :

Jan 11, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cemiplimab Three dose cohorts are planned and will follow a 3 + 3 dose-escalation design with cohort expansion. After completion of the above, three additional cohorts (A, B and C) of patients will be evaluated.	Drug: Cemiplimab Each patient will receive intralesional injections of cemiplimab every week (QW) or every other week (QOW) into the lesion at the assigned dose level for 5-12 weeks prior to scheduled surgery Other Names: REGN2810 Libtayo

Arm

Intervention/Treatment

Experimental: Cemiplimab

Three dose cohorts are planned and will follow a 3 + 3 dose-escalation design with cohort expansion. After completion of the above, three additional cohorts (A, B and C) of patients will be evaluated.

Drug: Cemiplimab

Each patient will receive intralesional injections of cemiplimab every week (QW) or every other week (QOW) into the lesion at the assigned dose level for 5-12 weeks prior to scheduled surgery

Other Names:

REGN2810

Libtayo

Outcome Measures

Primary Outcome Measures

Incidence, nature, and severity of dose limiting toxicities (DLTs) (if any) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 [From the first dose through day 28]
Dose levels 1-3
Incidence, nature, and severity of treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 [From the first dose through day 28]
Dose levels 1-3
Incidence and severity of TEAEs graded according to the NCI CTCAE v5 [From the first dose up to 90 days after the last dose]
Dose levels 1-3 and cohorts A - C
The incidence and severity of injection site reactions (ISRs) [From the first dose to 90 days after the last dose]
Dose levels 1-3 and cohorts A - C

Secondary Outcome Measures

Objective response rate (ORR) [At week 7; prior to week 13 surgery]
Determined by the investigator using the modified World Health Organization (WHO) criteria
Pathologic complete response rate (or end of treatment biopsies, for patients who decline surgery) [At time of surgery]
Major pathologic response rate (or end of treatment biopsies, for patients who decline surgery) [At time of surgery]
Cemiplimab concentration in serum over time [From the first dose up to 90 days after the last dose]
Incidence of anti-drug antibody (ADA) titers for cemiplimab [Up to 90 days after last dose]
Selection of the recommended dose of cemiplimab for further study based on clinical and pharmacokinetic (PK) observations [Up to 90 days after last dose]
The determination of the phase 2 recommended dose will be based primarily on clinical safety observations, according to the dose escalation scheme.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

Dose Escalation: History of recurrent resectable CSCC that satisfies conditions as defined in the protocol
Patient must have measurable disease in the index lesion, as defined by modified WHO criteria. Measurable disease is defined as at least one lesion that is at least 1 cm in both of the longest perpendicular diameters.
Eastern Cooperative Oncology Group (ECOG) performance status ≤1

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 (irAEs)
Prior treatment with an agent that blocks the programmed cell death

1 (PD-1)/ programmed cell death 1 ligand (PD-L1) pathway.

Prior treatment with other systemic immune modulating agent as defined in the protocol
M1 or N1, N2 (a, b, or c), or N3 CSCC or BCC. Patients with history of metastatic CSCC (distant or nodal), or metastatic BCC (distant or nodal) are excluded unless the disease-free interval is at least 3 years
Concurrent malignancies, other than those with negligible risk of metastasis or death. Patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL), are excluded.
Patients with a history of solid organ transplant
Has received a COVID-19 vaccination (initial series and booster) within 1 week of planned start of study medication

Note: Other protocol defined Inclusion/Exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Dermatology Specialists	Phoenix	Arizona	United States	85006
2	Regeneron Research Facility	Redwood City	California	United States	94063
3	Therapeutics Clinical Research	San Diego	California	United States	92123
4	Dermatology Associates of the Palm Beaches	Delray Beach	Florida	United States	33445
5	Regeneron Research Facility	Tampa	Florida	United States	33612
6	Regeneron Research Facility	Atlanta	Georgia	United States	30342
7	Regeneron Research Facility	Louisville	Kentucky	United States	40202
8	Northeast Dermatology Associates	Beverly	Massachusetts	United States	01915
9	NYU Langone	New York	New York	United States	10017
10	Rochester Dermatologic Surgery	Victor	New York	United States	14564
11	Duke Cancer Center	Durham	North Carolina	United States	27710
12	MD Anderson Cancer Center	Houston	Texas	United States	77030
13	INOVA Schar Cancer Institute	Fairfax	Virginia	United States	22031