Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer

This is a phase Ib/II clinical trial. DPX-E7 is a therapeutic vaccine, intended to treat
HPV-related head and neck, cervical or anal cancer. DPX-E7 is an investigational vaccine and
the FDA (the U.S. Food and Drug Administration) has not approved DPX-E7 vaccine as a
treatment for any disease.

DPX-E7 is being tested in humans for the first time. DPX-E7 is a kind of immunotherapy that
will make the immune system to elicit an anti-tumor response by generating CD8+ T-cells. CD8+
T-cells play a very important role in fighting against viral infections

Inclusion Criteria:

- Each patient must be positive for HLA-A*02 and meet all of the following inclusion
criteria to be enrolled in the study:

- Histologically or cytologically proven HPVOC or cervical cancer or anal cancer, based
on expression of HPV type16 in immunohistochemistry and/or HPV 16 DNA analysis by ISH
of tumor tissue from the primary or metastatic lesions.

- Incurable HPVOC, as defined by:

- Relapsed or progressive disease at the primary site and/or regional lymph nodes
after initial treatment (e.g. Surgery, radiotherapy or chemoradiotherapy) with no
potentially curative option (i.e. surgery or radiation); OR

- Distant metastasis

- Incurable cervical or anal cancer, as defined by:

- Relapsed or progressive disease at the primary site and/or regional lymph nodes
after initial treatment (e.g. systemic chemotherapy) with no potentially curative
option (i.e. surgery or chemoradiotherapy). Chemotherapy administered in
conjunction with primary radiation as a radiosensitizer will not be counted as a
systemic chemotherapy regimen; OR

- Distant metastasis refractory to initial treatment (at least one prior
chemotherapeutic regimen which can include a single chemotherapeutic, a
combination of chemotherapeutics, or biologic drugs such as bevacizumab).

- Accessible tumors for sequential biopsies Terminology Criteria for Adverse Events
Version 4.0 (CTCAE v4.03) to grade 1 or better (except for < grade 2 neuropathy,
alopecia, xerostomia, dysphagia, or mucositis);

- Age ≥ 18 years;

- Measurable disease, according to modified RECIST 1.1 and irRECIST (Appendix B & C);

- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 (Appendix A)

- Adequate bone marrow, liver and renal function, defined by:

- Hemoglobin ≥ 10 g/dL;

- Absolute neutrophil count (ANC) ≥ 1000/μL;

- Absolute lymphocyte count ≥ 400/μL;

- Platelet count ≥ 100,000/μL;

- ALT and AST ≤ 2.5 X upper limit of normal (ULN);

- Total bilirubin ≤ 1.5 X ULN; and

- Serum creatinine ≤ 1.5 X ULN;

- Women of child-bearing potential (WOCBP) must be willing to use acceptable means of
birth control;

- Men who could potentially father a child must also use birth control

- Signed informed consent

Exclusion Criteria:

- Radiotherapy for primary HPVOC within 8 weeks, or radiotherapy for any other reason
within 3 weeks prior to the first dose of trial treatment;

- Chemotherapy within 3 weeks prior to the first dose of trial treatment;Other cancer in
the past 5 years, except for carcinoma in situ of the cervix or bladder, or
non-melanomatous skin cancer;

- Inaccessible tumor or lack of consent for sequential biopsies

- Uncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are
radiographically unstable, symptomatic and/or requiring escalating doses of
corticosteroids);

- Active hepatitis, known HIV, or other condition that requires immunosuppressive
therapy, including current use of high dose systemic corticosteroids;

- Autoimmune disease, such as systemic lupus erythematosis or rheumatoid arthritis, that
is active and requires current immunosuppressive therapy;

- Active uncontrolled serious infection;

- WOCBP who have a positive β-hCG test or are breastfeeding.

- Acute or chronic skin disorders that would interfere with subcutaneous injection of
the vaccine or subsequent assessment of potential skin reactions;

- Allergies to any vaccine, that after discussion with Immunovaccine, are serious enough
to warrant exclusion from this study