VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer

PRIMARY OBJECTIVE:

To evaluate the effect of VX15/2503 alone and VX15/2503 in combination with immune checkpoint
inhibitors, ipilimumab or nivolumab, on the immune profile in the tumor microenvironment and
in peripheral blood.

SECONDARY OBJECTIVE:

To extend the previously reported safety profile of single agent VX15/2503 to the combination
of VX15/2503 and immune checkpoint inhibitors, ipilimumab or nivolumab, in patients with head
and neck squamous cell carcinoma.

OUTLINE: Participants are randomized to 1 of 6 groups.

GROUP A: Participants receive VX15/2503 intravenously (IV) over 60 minutes on day 1.
Beginning days 22-36, participants undergo standard of care surgery.

GROUP B: Participants receive VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes
on day 1. Beginning days 22-36, participants undergo standard of care surgery.

GROUP C: Participants receive VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes
on day 1. Beginning days 22-36, participants undergo standard of care surgery.

GROUP D: Participants receive nivolumab IV over 60 minutes on day 1. Beginning days 22-36,
participants undergo standard of care surgery.

GROUP E: Participants receive ipilimumab IV over 90 minutes on day 1. Beginning days 22-36,
participants undergo standard of care surgery.

GROUP F: Participants undergo standard of care surgery.

Inclusion Criteria:

- Stage I-IVA cytologically or histologically-proven head and neck squamous cell
carcinoma (HNSCC), p16 positive and negative allowed

- Oropharyngeal tumors must have p16 testing done

- Cancer confirmed to be surgically resectable, with surgery evaluation with planned
resection

- Archival tissue prior to treatment available from at most 6 months prior to study
enrollment. Otherwise new pre-treatment biopsy mandatory

- No prior treatment for HNSCC

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Absolute neutrophil count ≥ 1,500 cells/µL

- Platelets ≥ 100,000/µL

- Hemoglobin ≥ 9.0g/dL (may receive packed red blood cell [prbc] transfusion)

- Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

- Albumin ≥ 3.0 g/dL

- Serum creatinine ≤ 1.5 x ULN

- Calculated creatinine clearance of ≤ 50 mL/min

- International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low
molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic
dose for more than 2 weeks or with factor Xa level < 1.1 units/mL (U/mL) are allowed
on the trial

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures

- Ability to understand and willingness to sign a written informed consent document

- Female subjects of childbearing potential must agree to use adequate contraception
(e.g., hormonal or barrier method of birth control; abstinence) for the duration of
study treatment and 3 months after completion

- Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for
the duration of study treatment and 3 months after completion

- Female subjects of childbearing age must have a negative serum pregnancy test at study
entry

Exclusion Criteria:

- Poor venous access for study drug administration

- Nasopharynx cancer, cancer of unknown primary, sinonasal cancer

- Determined not to be a surgical candidate due to medical co-morbidities

- Treatment with chronic immunosuppressants (e.g., cyclosporine following
transplantation)

- Prior organ allograft or allogeneic bone marrow transplantation

- Subjects with any active autoimmune disease or history of known or suspected
autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll

- Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration. Inhaled or topical steroids and adrenal replacement
doses > 10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease

- Women who are pregnant or lactating

- Uncontrolled intercurrent illness including, but not limited to, human
immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
therapy, ongoing or active infection, symptomatic congestive heart failure (New York
Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Other medications, or severe acute/chronic medical or psychiatric condition, or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration, or may interfere with the interpretation of study
results, and in the judgment of the investigator would make the subject inappropriate
for entry into this study

- Clinical evidence of bleeding diathesis or coagulopathy

- Patients with prior malignancies are eligible if they have been disease free for > 5
years. Patients with prior in situ carcinomas are eligible provided there was complete
removal. Patients that have had prior treatment for HNSCC are not eligible

- Active bacterial or fungal infections requiring systemic treatment within 7 days of
treatment

- Use of other investigational drugs (drugs not marked for any indication) within 28
days or at least 5 half-lives (whichever is longer) before study drug administration

- History of severe hypersensitivity reactions to other monoclonal antibodies

- Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab

- No archival tissue available pre-study treatment, and repeat biopsy not feasible