Advanced Cutaneous Squamous Cell Carcinoma MedDRA version: 21.1 Level: PT Classification code 10077314 Term: Skin squamous cell carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Replimune, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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,
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with metastatic (nodal or distant) CSCC or with locally advanced CSCC as assessed by ORR according to central review.;Secondary Objective: •To estimate ORR for patients with locally advanced CSCC • To estimate ORR for patients with metastatic CSCC • To estimate ORR according to investigator review • To estimate ORR for patients having previously received systemic CSCC-directed therapy • To estimate ORR for patients not having previously received systemic CSCC-directed therapy • To estimate the duration of response (DOR) by central and investigator review • To estimate PFS by central and investigator review • To estimate the complete response (CR) rate by central review and investigator review • To estimate OS • To estimate disease-specific survival (DSS) • To estimate 3 year survival • To assess the safety and tolerability of cemiplimab alone and combined with RP1 • To assess the change of cemiplimab and cemiplimab combined with RP1 on quality of life using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30);Primary end point(s): The primary efficacy endpoint for this study is ORR according to central review: • RECIST version 1.1 will be used to determine ORR with the exception that PD must be confirmed by documentation of further progression 4-8 weeks following the initial assessment of PD. • In patients suspected of achieving a CR, tumor biopsies may be used in the final determination of complete versus PR. Patients who are deemed not evaluable (NE) by RECIST version 1.1 or inevaluable by the clinical or composite response criteria will be considered as not reaching PR/CR for ORR.;Timepoint(s) of evaluation of this end point: RECIST version 1.1 will be used to determine ORR. For the purposes of this study, patients should be re-evaluated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy outcome measures are: • ORR for patients with metastatic disease • ORR for patients with locally advanced disease • ORR by investigator assessments: - For patients in which all response assessments are performed on radiologic scans according to RECIST 1.1, the investigator’s response assessment for such patients will be RECIST 1.1 assessment from radiologic scans. - For patients in which all response assessments are performed on photographs according to Clinical Response Criteria (in Appendix 2), the investigator’s response assessment for such patients will be according to clinical assessments according to RECIST 1.1. • ORR for patients having previously received systemic CSCC-directed therapy • ORR for patients not having previously received systemic CSCC-directed therapy • Duration of response by investigator and central review • PFS by investigator and central review • OS • DSS • 3 year survival • CR rate by investigator and central review • Change in scores of patient-reported outcomes on EORTC QLQ-C30 • Safety and tolerability of cemiplimab alone and combined with RP1;Timepoint(s) of evaluation of this end point: RECIST version 1.1 will be used to determine ORR. For the purposes of this study, patients should be re-evaluated for response every 9 weeks. Confirmatory scans should also be obtained 4-8 weeks following initial documentation of objective response or progressive disease. | — |
Countries
Australia, Canada, France, United States
Contacts
Public ContactAnne-Marie Woodland
Replimune, Inc.
Outcome results
None listed