PRIMARY OBJECTIVE:
To evaluate the effect of the anti-SEMA4D monoclonal antibody VX15/2503 (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
pancreatic and colorectal cancer.
OUTLINE:
Patients are randomized to 1 of 4 arms.
ARM I: Patients undergo surgery.
ARM II: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60
minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.
ARM III: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and
ipilimumab IV over 90 minutes on day 1. Patients then proceed to surgery 22-36 days after
drug administration.
ARM IV: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and
nivolumab IV over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug
administration.
After completion of study treatment, patients are followed up at 90 days and then every 12
weeks thereafter.
Inclusion Criteria:
- For patients with pancreatic cancer:
- Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma
- Cancer confirmed to be surgically resectable, with surgery evaluation with
planned resection
- Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant
chemoradiation
- No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
- For patients with metastatic colorectal cancer:
- Stage IV histologically-proven colorectal adenocarcinoma
- Liver metastasis confirmed to be surgically resectable, with surgery evaluation
and planned resection; may have minimal extrahepatic disease that is determined
to be resectable
- Tumor must be confirmed to be microsatellite stable (MSS); if not already
reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we
will be able to perform this at Emory University
- No prior immunotherapy
- No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Absolute neutrophil count ≥ 1,500 cells/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9.0 g/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 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
- 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, 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, including pelvic cancer, are eligible if they have
been disease free for > 5 years; patients with prior in situ carcinomas are eligible
provided there was complete removal
- 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
