A phase I/IIa open label study to assess the safety, tolerability, immunogenicity and clinical activity of EI-201 mRNA immunotherapy given intravenously in subjects with recurrent or metastatic HPV16 positive carcinoma
- Conditions
- HPV16-positive (HPV16+) tumors (oropharyngeal cancer, cervical, vulvar, vaginal, anal, penile cancer)recurrent or metastatic HPV16-positive carcinoma10027655
- Registration Number
- NL-OMON56720
- Lead Sponsor
- eTheRNA immunotherapies
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 10
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 <= 1.5 x upper limit of normal (ULN) or creatinine-clearance
>= 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 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% of body surface area.
4. Subjects with serious intercurrent chronic or acute illness such as
pulmonary [severe asthma or chronic obstructive pulmonary disease (COPD)],
cardiac (New York Heart Association [NYHA] class III or IV), hepatic disease,
renal insufficiency or other illness considered by the Investigator to
constitute an unwarranted high risk for investigational drug treatment.
5. Subjects with known history of allergic reactions to contrast.
6. Subjects with significant psychiatric disabilities or seizure disorders.
7. Legal incapacity or limited legal capacity.
8. Subjects who have had a splenectomy.
9. Subjects with known hypersensitivity to any component of the Investigational
Medicinal Product and/or pembrolizumab (Cohort 2).
10. Prior treatment with therapeutic HPV vaccines. Subjects may have received a
preventive HPV vaccine.
11. Subjects who received an mRNA LNP based vaccine less than 30 days prior to
start of the therapy.
12. Concurrent second malignancy other than non-melanoma skin cancer or
controlled superficial bladder cancer. In the event of prior malignancies
treated surgically, the subject must be considered NED (no evidence of disease)
for a minimum of 3 years prior to enrollment.
13. Subjects on corticosteroid therapy > 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>COHORT 1<br /><br>Primary endpoint:<br /><br>• DLT, MTD, RP2D, SAEs, frequency and severity of AEs of escalating doses of<br /><br>EI-201 as monotherapy per dose level using NCI CTCAE 5.0<br /><br><br /><br>COHORT 2<br /><br>Primary endpoints:<br /><br>• DLT, MTD, RP2D, SAEs, AEs of EI-201 as add on to pembrolizumab using NCI<br /><br>CTCAE 5.0<br /><br>• ORR (based on CR/PR using RECIST v1.1 and iRECIST for highest dose level<br /><br>only). </p><br>
- Secondary Outcome Measures
Name Time Method