APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine the toxicities and establish the safety of multiple infusions of small
interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401
(APN401).

SECONDARY OBJECTIVES:

I. To determine the immunologic effects of multiple infusions of APN401. II. To document
clinical response and survival.

OUTLINE:

Patients receive siRNA-transfected peripheral blood mononuclear cells APN401 intravenously
(IV) over 30 minutes on days 1, 29, and 57 in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Inclusion Criteria:

- Patients with histologically confirmed inoperable, recurrent or metastatic malignant
solid tumors, deemed incurable, and who have either:

- Failed to respond to standard therapy or

- For whom no standard therapy is available or

- Refuse to receive standard therapies

- The study is intended to enroll patients with pancreatic and colorectal cancer;
patients with other types of solid tumors will require approval by the principal
investigator

- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

- Patients with treated, stable, and asymptomatic brain metastases are eligible

- Patients on every 3 or every 4 week systemic therapy programs must be at least 4 weeks
since treatment and recovered from any clinically significant toxicity experienced;
patients on weekly or daily systemic therapy programs and patients receiving radiation
must be at least 1 week since treatment and recovered from any clinically significant
toxicity experienced; must be at least 4 weeks and have recovered from major surgery

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

- White blood cells >= 3000/uL

- Platelets >= 100,000/uL

- Hematocrit >= 28%

- Creatinine =< 1.6 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper
limit of normal

- Bilirubin =< 1.6 mg/dL (except patients with Gilbert's syndrome, who must have a total
bilirubin less than 3.0 mg/dL)

- Albumin >= 3.0 g/dL

- International normalized ratio (INR) =< 1.5

Exclusion Criteria:

- Women must not be pregnant or breastfeeding; all women of childbearing potential must
have a blood test within 72 hours to rule out pregnancy; women of childbearing
potential and sexually active males must be strongly advised to use an accepted and
effective method of contraception; women of childbearing potential (WOCBP) must be
using an adequate method of contraception to avoid pregnancy throughout the study and
for 26 weeks after the last dose of investigational product, in such a manner that the
risk of pregnancy is minimized; sexually mature females who have not undergone a
hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive
months (i.e., who have had menses at some time in the preceding 24 consecutive months)
are considered to be of childbearing potential; women who are using oral
contraceptives, other hormonal contraceptives (vaginal products, skin patches, or
implanted or injectable products), or mechanical products such as an intrauterine
device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or
are practicing abstinence or where their partner is sterile (e.g., vasectomy) should
be considered to be of childbearing potential

- Untreated, progressing, or symptomatic brain metastases

- Autoimmune disease, as follows: patients with a history of inflammatory bowel disease
are excluded as are patients with a history of symptomatic disease (e.g., rheumatoid
arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus,
autoimmune vasculitis [e.g., Wegener's granulomatosis]); patients with motor
neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and
myasthenia gravis) are excluded; patients with a history of autoimmune thyroiditis are
eligible if their current thyroid disorder is treated and stable with replacement or
other medical therapy

- Any other malignancy from which the patient has been disease-free for less than 2
years, with the exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer or carcinoma in situ of the cervix

- Other ongoing systemic therapy for cancer, including any other experimental treatment;
these include concomitant therapy with any of the following: IL-2, interferon,
ipilimumab, pembrolizumab, nivolumab, or other immunotherapy; cytotoxic chemotherapy;
and targeted therapies

- Ongoing requirement for an immunosuppressive treatment, including the use of
glucocorticoids or cyclosporine, or with a history of chronic use of any such
medication within the last 4 weeks before enrollment; patients are excluded if they
have any concurrent medical condition that requires the use of systemic steroids (the
use of inhaled or topical steroids is permitted)

- Infection with human immunodeficiency virus (HIV)

- Active infection with hepatitis B; active or chronic infection with hepatitis C

- Clinically significant pulmonary dysfunction, as determined by medical history and
physical examination; patients with a history of pulmonary dysfunction must have
pulmonary function tests with a forced expiratory volume in 1 second (FEV1) >= 60% of
predicted and a diffusing capacity of the lung for carbon monoxide (DLCO) >= 55%
(corrected for hemoglobin)

- Clinically significant cardiovascular abnormalities (e.g., congestive heart failure or
symptoms of coronary artery disease), as determined by medical history and physical
examination; patients with a history of cardiac disease must have a normal cardiac
stress test (treadmill, echocardiogram, or myocardial perfusion scan) within the past
6 months of study entry

- Active infections or oral temperature > 38.2 degrees Celsius (C) within 48 hours of
study entry

- Systemic infection requiring chronic maintenance or suppressive therapy

- Patients are excluded for any underlying medical or psychiatric condition, which in
the opinion of the investigator, will make treatment hazardous or obscure the
interpretation of adverse events, such as a condition associated with frequent rashes
or diarrhea