A study evaluating the clinical benefit of Cemiplimab versus Cemiplimab in combination with RP1 in patients with skin cancer
- Conditions
- Advanced Cutaneous Squamous Cell CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.1Level: PTClassification code 10077314Term: Skin squamous cell carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2018-003964-30-FR
- Lead Sponsor
- Replimune, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 240
1. Voluntary agreement to provide written informed consent and willingness and ability to comply with protocol requirements.
2. Histologically confirmed diagnosis of CSCC that is locally advanced or metastatic.
3. At least 1 lesion that is measurable and injectable by study criteria (tumor of =1cm in longest
diameter or =1.5 cm in shortest diameter for lymph nodes).
If a previously radiated lesion is to be followed as a target lesion, progression of that lesion
must be confirmed by biopsy after radiation therapy. Previously radiated lesions may be
followed as non-target lesions if there is at least 1 other measurable target lesion.
4. Eastern Cooperative Oncology Group (ECOG) performance status =1.
5. Male or female =18 years old.
6. Hepatic function:
a. Total bilirubin =1.5 x upper limit of normal (ULN); (if liver metastases =3 x ULN). Patients
with Gilbert’s Disease and total bilirubin up to 3 x ULN may be eligible after
communication with and approval from the medical monitor.
b. Transaminases (ALT or AST) =3 x ULN (or =5.0 x ULN, if liver metastases)
c. Alkaline phosphatase (ALP) =2.5 x ULN (or =5.0 x ULN, if liver or bone metastases)
Note for patients with hepatic metastases who wish to enroll: If transaminase levels
(AST and/or ALT) are >3 x but =5 x ULN, total bilirubin must be =1.5 x ULN. If total bilirubin
is >1.5 x but =3 x ULN, both transaminases (AST and ALT) must be =3 x ULN.
7. Renal function: Serum creatinine =1.5 x ULN or estimated creatinine clearance =30cc/min
8. Bone marrow function:
a. Hemoglobin =9.0 g/dL
b. Absolute neutrophil count (ANC) =1.5 x 109/L
c. Platelet count =100 x 109/L
9. Prothrombin time (PT) = 1.5 x ULN (or international normalization ratio [INR] = 1.3) and
partial thromboplastin time (PTT) or activated PTT (aPTT) = 1.5 x ULN.
10. Anticipated life expectancy >12 weeks.
11. Females of childbearing potential who have a negative serum pregnancy test at screening
and urine on Cycle 1 Day 1 prior to dosing.
12. Female subjects of childbearing potential who are willing to use a highly effective method
of birth control (which must include at least a barrier method) or who are surgically sterile
or abstain from heterosexual activity for the course of the study and for 6 months after last
dose of study drug.
13. Male subjects of reproductive potential who agree to use a highly effective method of
contraception during sexual contact with females of childbearing potential (which must
include at least a barrier method) starting from the first dose of study drug to 6 months after
the last dose of study drug and also agree to abstaining from donating sperm during this
period.
14. Screening electrocardiogram (ECG) without evidence of acute ischemia or prolonged QT
interval > 440ms.
15. Baseline troponin < 0.06 ng/mL.
16. Baseline pulse oximetry with pO2 = 92% on room air.
17. Locally advanced only: Surgery must be deemed contraindicated in the opinion either a
medical oncologist with experience in cutaneous malignancy management or a
dermatologist, or a head and neck surgeon, or multi-disciplinary disease management
team.
18. Locally advanced only: Patients must be deemed as not appropriate for radiation therapy.
This must include the opinion of a radiation oncologist or either a medical oncologist, head
and neck surgeon or dermatologist with expertise in cutaneous malignancies, or a multidisciplinary
team.
19. All patients must consent to provide archived or newly obtained tumor material (either
formalin-fixed,
1. Prior treatment with an oncolytic therapy.
2. Patients with active significant herpetic infections or prior complications of HSV-1 infection
(e.g. herpetic keratitis or encephalitis).
3. Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals
with known anti-herpetic activity (e.g. acyclovir).
4. 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) or has a diagnosis of immunodeficiency disorders
(such as human immunodeficiency virus (HIV) disease or organ transplantation or
hematologic malignancies associated with immune suppression).
Note: 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. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
6. Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant
therapy within 3 years. Examples of immune modulating agents include therapeutic anti-cancer vaccines,
cytokine treatments (other than G-CSF or erythropoietin), or agents that target CTLA-4,
4-1BB (CD137), PI 3-K-delta, or OX-40.
7. Untreated brain metastasis(es) that may be considered active.
8. Immunosuppressive corticosteroid doses (> 20 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of cemiplimab.
9. Known infection including active infection with hepatitis B virus (HBV), hepatitis C virus
(HCV) or HIV.
10. History of interstitial lung disease (ILD)/pneumonitis within the last 5 years or a history of
ILD/pneumonitis requiring treatment with systemic steroids.
11. History of myocarditis or congestive heart failure (as defined by the New York Heart
Association Functional Classification III or IV), or unstable angina, serious uncontrolled
cardiac arrhythmia, uncontrolled infection or myocardial infarction within 6 months of dosing.
12. Grade = 3 hypercalcemia at time of enrollment.
13. Any systemic anticancer treatment (chemotherapy, targeted systemic therapy,
photodynamic therapy), investigational or standard of care, within 30 days of the initial
administration of RP1 or cemiplimab or planned to occur during the study period (patients receiving bisphosphonates or denosumab are not excluded), radiation therapy within 14
days of initial administration of cemiplimab or planned to occur during the study period.
14. History of documented allergic reactions or acute hypersensitivity reaction attributed to
antibody treatments.
15. Patients with allergy or hypersensitivity to RP1 or cemiplimab or to any of the excipients
must be excluded. Specifically, because of the presence of trace components in
cemiplimab, patients with allergy or hypersensitivity to doxycycline or tetracycline are
excluded.
16. Patients who are breast feeding.
17. Concurrent malignancy other than CSCC and/or history of malignancy other than CSCC
within 3 years of date of first planned dose of cemiplimab, except for tumors with negligible
risk of metastasis or death. Examples include: adequately treated BCC of the skin,
carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast, or low-risk early
stage prostate adenocarcinoma (T1-T2aN0M0 and Gleason score =6 and prostate specific
antigen [PSA] =10 ng/mL) for which the man
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method