A study evaluating the clinical benefit of cemiplimab versus cemiplimab in combination with RP1 in patients with skin cancer
- Conditions
- Advanced Cutaneous Squamous Cell CarcinomaMedDRA version: 21.1Level: PTClassification code 10077314Term: Skin squamous cell carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003964-30-IT
- Lead Sponsor
- Replimune, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
1. Voluntary agreement to provide written informed consent and willingness and ability to comply with protocol requirements.
2. Histologically confirmed diagnosis of locally advanced or metastatic (nodal or distant) CSCC by local pathology report. Metastatic (nodal or distant) disease is defined as disseminated disease distant to the
initial/primary site of diagnosis. The locally recurrent disease is defined as previously treated disease (with either surgery, radiotherapy, or systemic therapy) and is not amenable to either curative surgery, radiotherapy, or concurrent chemoradiotherapy treatment.
3. At least 1 measurable lesion and lesion(s) that are injectable. There is no minimum tumor size for injection, provided there are injectable tumors that are in the aggregate of = 1 cm at baseline.
4. Eastern Cooperative Oncology Group (ECOG) performance status =1 (Appendix 4).
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, if serum creatinine >1.5XULN, calculated creatinine clearance =30mL/min (using Cockcroft).
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. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception methods for 6 months after the last dose of cemiplimab or cemiplimab and RP1 combination treatment. In addition,
male patients must refrain from donating sperm during this study treatment and for up to 6 months after the last dose of cemiplimab or cemiplimab and RP1 combination treatment. For a definition of highly effect contraceptive methods and instructions of patients and partners, see Section 9.3.4.9.
12 . Locally advanced CSCC only (Surgery) must be deemed as not appropriate candidates for curative surgery in the opinion of either a medical oncologist with experience in cutaneous malignancy management, a dermatologist, a head and neck surgeon, or a multidisciplinary disease management team, or documented to have refused surgery despite consultation.
13 . Locally advanced CSCC only (Radiotherapy): Patients must be deemed as not appropriate candidates for curative radiation therapy or documented as having refused radiotherapy despite consultation. This must include the opinion of either a radiation oncologist, a medical oncologist, a head and neck surgeon, a dermatologist with expertise in cutaneous malignancies, or a multidisciplinary team.
14. All patients must consent to provide archived (within 12 months [6 months preferred] of screening date)
1.Prior treatm with an oncolytic therap
2.Pt with active significant herpetic infections or prior complications of HSV-1infection(e.g.herpetic keratitis or encephalitis or disseminated herpes infection)
3.Pt who require intermittent or chronic use of systemic(oral or IV)anti-virals with known antiherpetic activity(e.g.acyclovir)
4.Ongoing or recent(within5y) evidence of significant autoimmune disease that required treatm with systemic immunosuppressive treatms,which may suggest risk for imAE or has a diagnosis of immunodeficiency disorders(such as HIV disease or organ transplantation or hematologic malignancies associated with immune suppression)
5.Prior treatm with an agent that blocks thePD-1/PD-L1pathway
6.Prior treatm with other immune modulating agents other than as adjuvant or neoadjuvant therapy within3y.Examples of immune modulating agents include therapeutic anti-cancer vaccines,cytokine treatms(other than G-CSFor erythropoietin),or agents that targetCTLA-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(>10mg prednisone daily or equivalent)within2w prior to randomisation
9.Pt who has acute or chronic active hepatitisB or known history of hepatitisB(defined as hepatitisB surface antigen[HBsAg]reactive)or HCV or HIV infection
10.Active infection requiring systemic therapy with14dd prior to randomisation
11.History of interstitial lung disease(ILD)/pneumonitis within the last 5y or a history of ILD/pneumonitis requiring treatm with systemic steroids
12.History of myocarditis or congestive heart failure(as defined by the NYHA Classification III or IV),or unstable angina,serious uncontrolled cardiac arrhythmia,uncontrolled infection or myocardial infarction within 6 months of randomisation
13.Grade>=3hypercalcemia at time of enrollment
14.Any systemic anticancer treatm(chemotherapy,targeted systemic therapy,photodynamic therapy),investigational or standard of care, within 28dd of randomisation or planned to occur during the study period(Pt receiving bisphosphonates or denosumab are not excluded).Radiation therapy within14dd of randomisation or planned to occur during the study period.Any major surgical procedure <=28dd before randomization.Pt must have recovered adequately from the toxicity and/or complications from prior interventions prior to randomization
15.Was administered a live vaccine<=28dd before randomisation
16.History of documented allergic reactions or acute hypersensitivity reaction attributed to ab treatms
17.Pt with allergy or hypersensitivity toRP1or cemiplimab's excipients must be excluded.Specifically,cause of the presence of trace components in cemiplimab,Pt with allergy or hypersensitivity to doxycycline or tetracycline are exclud
18.Female who has a positive serumß-hCG pregnancy(at screening<=72h prior to first study treatm)and urine pregnancy test(Cycle1Day1)or is breast feeding or planning to become pregnant
19.Concurrent malignancy other thanCSCCand/or history of malignancy other thanCSCC within 3y of date of first planned dose of cemiplimab,except for tumors with negligible risk of metastasis or death.Examples are provided in section 4.2.2. of the study protocol
20.Any acute or chronic psychiatric problems or substance abuse disorders that in the opinion of the investigator,would interfer with the pt cooperating with the requirements of the study
21.Any medical co-morbidity,physical examination finding,or metabolic
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