RecruitingPhase 1NCT03690986

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

Integrated Pilot Biomarker Trial of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer

Sponsor

Emory University

Enrollment

50 participants

Start Date

Nov 1, 2018

Study Type

INTERVENTIONAL

Conditions

Squamous Cell Carcinoma of the Head and Neck

Summary

This phase I trial studies how well anti-semaphorin 4D (SEMA4D) monoclonal antibody VX15/2503 (VX15/2503) with or without ipilimumab and/or nivolumab work in treating patients with stage I-IVA head and neck squamous cell cancer. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.

Eligibility

Min Age: 18 Years

Inclusion Criteria20

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 Criteria18

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
Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate risk prostate cancer, or in situ carcinoma fully resected) unless disease free for a minimum of one year
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