HPV16-positive (HPV16+) tumors (oropharyngeal cancer, cervical, vulvar, vaginal, anal, penile cancer) recurrent or metastatic HPV16-positive carcinoma
Conditions
Interventions
None listed
Sponsors
eTheRNA immunotherapies
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria to be assessed at Screening: 1. Age greater than or equal to 18 years. 2. Cohort 1: Confirmed recurrent and/or metastatic (R/M) HPV16+ cancer (including oropharyngeal, cervical, vulvar, vaginal, anal, penile cancer) based on expression analysis of HPV type 16 in tumor tissue by HPV 16 ISH or HPV E1 PCR. Cancer must have progressed after at least 1 available standard therapy for incurable disease, or the subject is intolerant to or refuses standard therapy(ies) or has a tumor for which no standard therapy(ies) exists. Cohort 2: Confirmed R/M HPV16+ oropharyngeal cancer (based on expression of HPV type 16 in tumor tissue by HPV 16 ISH or HPV E1 PCR), and eligible for 1st line monotherapy pembrolizumab treatment OR subjects with confirmed incurable R/M anogenital HPV16+ cancer (cervical, anal, penile, vulvar, or vaginal cancer) confirmed by HPV 16 ISH or HPV E1 PCR. Maximum 2 previous systemic therapies with chemotherapy and/or targeted therapies for recurrent and/or metastatic disease, no prior aPD(L)-1, and a CPS>1. 3. Life expectancy of at least 12 weeks. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al, 2009). 6. Willing and able to give written informed consent. 7. Willing and able to attend the scheduled study visits and to comply with the study procedures, treatment schedule, laboratory test and other requirements of the study. 8. Subjects entering the study will need to consent to provide a tumor tissue sample (formalin fixed paraffin embedded blocks/slides less than 2 months old or older only upon approval by Sponsor) or a fresh biopsy before the first dose of the study treatment and a mandatory biopsy at Week 6 (Cohort 1) or Week 9 (Cohort 2) post start of treatment. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. 9. Adequate hematologic function with: a) white blood cell (WBC) count >= 3,000 mm³ b) hemoglobin >= 9 g/dL c) platelets >= 75,000/mm³ d) lymphocyte count >=500 cells/mm3 10. Adequate renal and hepatic function with: a) serum creatinine = 40 mL/minute using the Cockcroft-Gault formula b) alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST) <= 1.5 x ULN (subjects with liver metastasis can have up to 5 x ULN c) bilirubin < 2.0 mg/dL (except for subjects with Gilbert*s disease) 11. Adequate coagulation parameters with: a) Prothrombin international normalized ratio (INR) < 1.5 b) Partial thromboplastin time < 1.5 x ULN 12. Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. The Investigator shall review contraception methods and the time period that contraception must be followed. 13. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) b) A WOCBP (defined as < 2 years after last menstruation or not surgically sterile) must have a negative highly sensitive pregnancy test at screening (serum) and
Exclusion criteria
Exclusion criteria: Exclusion criteria to be assessed at Screening: 1. Subjects treated with any investigational agent within the past 4 weeks before the start of therapy are excluded. 2. Grade 3 or 4 peripheral neuropathy at time of screening. 3. Subjects with active or history of autoimmune disease or immune deficiency such as, but not restricted to, myasthenia gravis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, rheumatoid arthritis or multiple sclerosis, with the following exceptions: - endocrine autoimmune disorders (i.e., autoimmune hypothyroidism who are on thyroid replacement hormone, type 1 diabetes, Addison*s disease, etc.) - controlled eczema, psoriasis, lichen simples or vitiligo with dermatological manifestations only - rash 10 mg prednisone (or equivalent) or other immunosuppressive agents such as azathioprine or cyclosporine A (but not limited to these) are excluded on the basis of potential immune suppression. 14. Presence of an active acute or chronic infection, including symptomatic urinary tract infection, human immunodeficiency virus (as determined by enzyme linked immunosorbent assay and confirmed by Western Blot) or viral hepatitis (as determined by hepatitis B antigen and hepatitis C serology). 15. Subject is pregnant, intending to become pregnant or is currently breast-feeding. 16. Subject testing positive for SARS-CoV-2 infection as detected by nasal real time polymerase chain reaction (RT-PCR) or subjects who have been in contact with SARS-CoV-2 infected individuals in the 2 weeks prior to first dosing of IMP. Subjects presenting any signs or symptoms of SARS-CoV-2 infection as detected at screening and/or baseline following careful physical examination (e.g., cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc.) will also be excluded. In addition, any other locally applicable standard diagnostic criter
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| COHORT 1 Primary endpoint: • DLT, MTD, RP2D, SAEs, frequency and severity of AEs of escalating doses of EI-201 as monotherapy per dose level using NCI CTCAE 5.0 COHORT 2 Primary endpoints: • DLT, MTD, RP2D, SAEs, AEs of EI-201 as add on to pembrolizumab using NCI CTCAE 5.0 • ORR (based on CR/PR using RECIST v1.1 and iRECIST for highest dose level only). | — |
Secondary
| Measure | Time frame |
|---|---|
| COHORT 1 Secondary endpoints: • Number of immune responders to EI-201 per dose level • ORR (based on CR/PR using RECIST v1.1 and iRECIST) Exploratory endpoints: • Changes from baseline in ctHPV16 DNA per dose level • Dosing confirmation of HPV E6 mRNA and the LNP component Coatsome SS-EC • Tumor biopsy to assess changes in the tumor microenvironment induced by EI-201 administration compared to baseline COHORT 2 Secondary endpoints: • Immune response to EI-201 as add on to pembrolizumab at each visit • BOR based on CR, SD, PR, progressive disease (PD) and overall response at each visit by RECIST 1.1 and iRECIST • ORR (based on CR/PR using iRECIST and RECIST 1.1 for all other dose levels) • Overall survival (OS) Exploratory endpoints: • Change and percentage change from baseline in ctHPV DNA levels per dose level and tumor type • Tumor biopsy to assess changes in the tumor microenvironment induced by EI-201 administration as add on to pembrolizumab compared to baseline • Associations between antitumor effect and biomarkers, such as ctHPV16 DNA or immune response • Dosing confirmation of HPV E6 mRNA and the LNP component Coatsome SS-EC | — |
Countries
Netherlands
Outcome results
None listed