IRX-2 Regimen Combined With Nivolumab in Recurrent/Metastatic Solid Tumors
IRX-2 Regimen Combined With Nivolumab in Recurrent/Metastatic Solid Tumors
This study is to determine the safety of IRX-2 Regimen combined with Nivolumab in patients
 with recurrent metastatic solid tumors. Researchers believe that this combination will have a
 tolerable safety profile and will increase the response rate in comparison to Nivolumab
 alone.
The first phase of this trial is to establish the safety of IRX-2 Regimen combined with
 Nivolumab. The IRX-2 Regimen is a 21-day regimen of cyclophosophamide on Day 1 and
 subcutaneous IRX-2 injections for 10 days between Days 4 and 18. If no dose limiting
 toxicities (DLTs) are observed during the first 4 weeks of treatment, the enrollment will
 continue in a dose expansion phase. If there is a study treatment related DLT in 1 of 6
 patients, the same dose will be investigated at the dose expansion cohorts. If study
 treatment related DLT is observed in 2 of 6 patients, accrual will be stopped and new dose
 levels or treatment sequences will be considered.
Inclusion Criteria:

 -  At least 18 years of age

 -  Participants must have histologically or cytologically confirmed renal cell
 carcinoma,urothelial carcinoma, non-small cell lung cancer, squamous cell carcinoma of
 the head and neck or melanoma.

 -  Participants must have recurrent or metastatic disease that is not amenable to local
 therapy with curative intent (surgery or radiation therapy with or without
 chemotherapy).

 -  Must be willing and able to give informed consent and adhere to protocol therapy;
 written informed consent and any locally required authorization must be obtained from
 the participant prior to performing any protocol-related procedures, including
 screening evaluations

 -  Prior exposure to PD-1/PD-L1 inhibitor monotherapy, or prior exposure to CTLA-4
 inhibitor monotherapy is allowed.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

 -  Adequate normal organ and marrow function

 -  Participants who are receiving therapeutic anti-coagulant therapy are eligible.

 -  Palliative radiation therapy is allowed to non-target lesions at the discretion of the
 treating physician.

 -  Participants must have measurable disease, defined as at least one lesion that can be
 accurately measured in at least one dimension (longest diameter to be recorded) as
 outlined in RECIST version 1.1.

 -  Life expectancy of greater than 3 months.

 -  Female participants of childbearing potential must have a negative serum pregnancy
 test within 7 days prior to treatment.

 -  Body weight must be greater than 66 pounds.

 Exclusion Criteria:

 -  Prior exposure to a combination of IRX-2 regimen, PD-1/PD-L1 inhibitors and CTLA-4
 inhibitors are excluded. Prior exposure to PD-1/PD-L1 inhibitors is allowed.

 -  Radiation therapy with a curable intent within 30 days of first dose of study
 treatment is excluded. However, radiation therapy with a palliative intent is allowed
 to treat after 14 days from the last dose of radiation.

 -  Any medical contraindications or previous therapy that would preclude treatment with
 the IRX-2 Regimen, or nivolumab.

 -  Any unresolved toxicity Grade 2 or greater from previous anticancer therapy with the
 exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
 criteria.

 -  Participants with irreversible toxicity not reasonably expected to be exacerbated by
 treatment with IRX-2, or nivolumab may be included only after consultation with the
 study physician.

 -  Active or prior documented autoimmune or inflammatory disorders

 -  Current or prior use of immunosuppressive medication within 14 days before the first
 dose of study treatment. Some exceptions apply.

 -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
 first dose of study treatment. Note: Local surgery of isolated lesions for palliative
 intent is acceptable.

 -  History of allogenic organ transplantation.

 -  Symptomatic cardiopulmonary disease, coronary artery disease, serious arrhythmia or
 chronic lung disease. Participants with these conditions who are stable with
 relatively minor symptoms and who are appropriate candidates for systemic treatments
 need not be excluded.

 -  Myocardial infarction within the last 3 months.

 -  Known infection with hepatitis B, hepatitis C, or HIV.

 -  Signs or symptoms of systemic infection (use of antibiotics to treat superficial
 infection or contamination of tumor shall not, by itself, be considered evidence of
 infection).

 -  Clinically significant gastritis or peptic ulcer disease

 -  Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months.

 -  Allergy to ciprofloxacin (or other quinolones).

 -  Previous diagnosis of invasive cancer from which the individual is not disease-free
 AND that has required treatment within the past 3 years, except for superficial skin,
 cervical cancer in-situ, or early stage prostate or bladder cancer (i.e. treatment
 with curative intent and long term disease-free expectations).

 -  History of leptomeningeal carcinomatosis

 -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
 excipients.

 -  Female participants who are pregnant or breastfeeding or male or female participants
 of reproductive potential who are not willing to employ effective birth control from
 screening to 1 year after the last dose of study treatment.