E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Incurable recurrent or metastatic (R/M) HPV16-positive (HPV16+) tumors (e.g. oropharyngeal cancer, cervical, vulvar, vaginal, anal, penile cancer, etc.) |
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E.1.1.1 | Medical condition in easily understood language |
Incurable recurrent or spread cancer caused by the human papillomavirus type 16 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047777 |
E.1.2 | Term | Vulvar cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061424 |
E.1.2 | Term | Anal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046885 |
E.1.2 | Term | Vaginal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034299 |
E.1.2 | Term | Penile cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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). |
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E.5.1.1 | 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 |
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E.5.2 | 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) |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose escalation and dose expansion |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |