Incurable recurrent or metastatic (R/M) HPV16-positive (HPV16+) tumors (e.g. oropharyngeal cancer, cervical, vulval, vaginal, anal, penile cancer, etc.) MedDRA version: 21.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (
Conditions
Sponsors
eTheRNA immunotherapies NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age greater than or equal to 18 years. - Cohort 1: Confirmed recurrent and/or metastatic (R/M) HPV16+ cancer (including oropharyngeal, cervical, vulval, 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 (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 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. - At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al, 2009). - 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. - Adequate hematologic function - Adequate renal and hepatic function - Adequate coagulation parameters Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: - Grade 3 or 4 peripheral neuropathy at time of screening. - Subjects with active or history of autoimmune disease or immune deficiency. - Subjects with serious intercurrent chronic or acute illness. - Subjects who have had a splenectomy. - Subjects with known hypersensitivity to any component of the Investigational Medicinal Product and/or pembrolizumab (Cohort 2). - Prior treatment with HPV therapeutic vaccines. Subjects may have received a preventive HPV vaccine. - Subjects who received an mRNA LNP based vaccine less than 30 days prior to start of the therapy. Additional Criteria for Cohort 2: - Chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks prior to start of treatment with EI-201 for subjects with anogenital cancers. - Subjects who have received prior systemic therapy and/or active immunotherapy for HNSCC, such as antigen loaded dendritic cells, chimeric antigen receptor (CAR) T cells, or checkpoint inhibitors are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Cohort 1: - To assess the immune response following EI-201 administration in subjects with incurable R/M HPV16+HPV16+ oropharyngeal and R/M HPV16+ anogenital tumors - To assess the preliminary anti tumor activity of IV administration of EI-201 as monotherapy in subjects with incurable R/M HPV16+ oropharyngeal and anogenital tumors Cohort 2: - To assess the immunogenicity of EI-201 as add on to pembrolizumab in subjects with incurable R/M HPV16+HPV16+ oropharyngeal HNSCC and R/M HPV16+ anogenital tumors - To assess additional anti-cancer activity of EI-201 as add on to pembrolizumab in subjects with incurable R/M HPV16+HPV16+ oropharyngeal HNSCC and R/M HPV16+ anogenital tumors;Main Objective: Cohort 1: To assess the safety and tolerability of IV administration of EI-201 as monotherapy in subjects with incurable R/M HPV16+ oropharyngeal and anogenital tumors and to select a starting dose of EI-201 for Cohort 2 Cohort 2: To assess the safety and tolerability of IV administration of EI-201 as add on to pembrolizumab in subjects with incurable R/M HPV16+ oropharyngeal and anogenital tumors;Primary end point(s): Cohort 1: 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: DLT, MTD, RP2D, SAEs, AEs of EI-201 as add on to pembrolizumab using NCI CTCAE 5.0 Cohort 2: ORR (based on CR/PR using RECIST v1.1 and iRECIST for highest dose level only). ;Timepoint(s) of evaluation of this end point: Cohort 1: At screening, day 1, day 8, day 15, day 22, day 29, day 43, day 50 Cohort 2: At screening, day 1, day 8, day 15, day 22, day 29, day 50, day 57, day 71, day 92, day 113, day 134, day 155, day 69, day 183 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cohort 1: Number of immune responders to EI-201 per dose level Cohort 1: ORR (based on CR/PR using RECIST v1.1 and iRECIST) Cohort 2: Immune response to EI-201 as add on to pembrolizumab at each visit Cohort 2: - 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 dose levels) - Overall survival (OS);Timepoint(s) of evaluation of this end point: Cohort 1: At screening, day 1, day 8, day 15, day 22, day 29, day 43, day 50 Cohort 2: At screening, day 1, day 8, day 15, day 22, day 29, day 50, day 57, day 71, day 92, day 113, day 134, day 155, day 69, day 183 | — |
Countries
Belgium, Germany, Poland
Contacts
Public ContactConsultant Development
eTheRNA immunotherapies NV
Outcome results
None listed