ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer

This is an investigator-initiated prospective clinical study of patients with stage I-IV squamous cell carcinoma of the oropharynx (OPSCC) who are to undergo ablative transoral robotic surgery (TORS).

There is a vaccination group and a control group in this study.

Subjects in the control group will not receive the vaccination and will only be followed after TORS surgery for additional research blood tests to measure how their immune system is working.

Subjects in the vaccination group will receive two vaccinations prior to surgery. The first dose will be about 33 days before surgery, and the second will be about 14 days before surgery.

Participation in this study will also include allowing the research team to take several blood samples from the subject at various times before, during, and after treatment for his/her cancer.

Vaccination subjects will be monitored closely after treatment and includes 6 months of oral antibiotics.

• ADXS11-001 (ADXS-HPV) (Biological), also known as ADXS11-001, ADXS-HPV: ADXS11-001 (ADXS-HPV) is a live attenuated Listeria monocytogenes (Lm)-LLO immunotherapy developed for the treatment of HPV-associated dysplasia and malignancy.

Primary outcomes

• HPV-Specific T Cell Response Rate [At time of surgery]: Response rate defined as proportion of participants with a >2-fold increase in HPV-specific T cell response from baseline to time of surgery.
• Number of Participants With Any Grade 3 or 4 Toxicity [Assessed up to 30 Days after surgery]: Degree of toxicity assessed according to NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria.

Secondary outcomes

• HPV-Specific T Cell Response Rate [Assessed up to 3 months after surgery]: Response rate defined as proportion of participants with a >2-fold increase in HPV-specific T cell response from baseline to 3 months after surgery.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* The patient has newly-diagnosed, biopsy proven squamous cell carcinoma of Stage I-IV (T1-3, N0-2b) of the oropharynx.
* The patient's tumor is HPV positive by PCR or ISH assay of tumor biopsy.
* The patient is able/eligible to undergo treatment with transoral robotic surgery (TORS) with or without neck dissection and with or without adjuvant radiation therapy or chemoradiation.
* The patient is able to understand and give informed consent.
* The patient is at least 18 years old.
* The patient's ECOG performance status is </= 2.

Exclusion Criteria:

* The patient has had prior head and neck squamous cell carcinoma (HNSCC), with the exception of superficial cutaneous basal cell or squamous cell carcinomas.
* The patient has active cancer in another part of the body, with the exception of superficial cutaneous basal cell or squamous cell carcinomas
* If a cancer survivor, the disease free interval is less than 3 years, with the exception of superficial cutaneous basal cell or squamous cell carcinomas.
* If a cancer survivor the patient received prior systemic chemotherapy or radiotherapy
* If prior standard-of-care pre-treatment biopsy is inadequate for analysis by immunohistochemistry, and the patient is unwilling to undergo an additional biopsy procedure.
* The patient is a prisoner.
* The patient has a psychiatric illness or developmental delay which would interfere with understanding of the study and provision of informed consent.
* The patient has previously received definitive surgical, radiation, or chemoradiation treatment for HNSCC.
* The patient has a history of HIV or other known cause of immunosuppression, or is actively taking immunosuppressive medications due to organ transplantation, rheumatoid disease, or other medical conditions.
* Patient is allergic to naproxen or Ibuprofen.
* The patient has a history of liver disease.
* The patient has a contraindication (e.g. sensitivity/allergy) to both trimethoprim/sulfamethoxazole and ampicillin.
* The patient has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g. Port-a-Cath or Mediport) are permitted.
* Patients who are receiving or may receive future treatment with PI3K or TNFα inhibitors.
* Patients who have undergone a major surgery, including surgery for a new artificial implant and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment. Sponsor must be consulted prior to enrolling subjects on the study who recently had a major surgery or have new artificial implant, and/or devices.
* Patients who have a history of listeriosis or prior ADXS11-001 therapy.
* Patients with a known allergy to any component of the study treatment formulations.
* Pregnancy. The effects of this vaccine on the developing human fetus are unknown. For this reason women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation, Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Participant flow

Outcome results

• HPV-Specific T Cell Response Rate (Primary), Number, proportion of participants: Treatment-Vaccine Group 0.333 (0.075 to 0.701); Control Group
• Number of Participants With Any Grade 3 or 4 Toxicity (Primary), Count of participants, Participants: Treatment-Vaccine Group 5; Control Group 1
• HPV-Specific T Cell Response Rate (Secondary), Number, proportion of participants: Treatment-Vaccine Group 0.625 (0.245 to 0.915); Control Group 0.75 (0.194 to 0.994)

Adverse events

Time frame: Up to 3 year post treatment for the vaccinated group or post surgery for the control group.

Serious adverse events by term

Other adverse events by term

46 more terms not shown.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-01-09)

• Andrew G Sikora, MD PhD, Study chair, Baylor College of Medicine
• Brett Miles, MD, Principal investigator, Icahn School of Medicine at Mount Sinai