ALT-803 in Patients With Advanced Pancreatic Cancer Conjunction With Gemcitabine and Nab-Paclitaxel

The purpose of this study is to evaluate the safety and tolerability of escalating doses, to
identify the Maximum Tolerated Dose (MTD) and designate a dose level for Phase II study
(RP2D) of ALT-803 administered in combination with gemcitabine and nab-paclitaxel in
patients with advanced pancreatic cancer.

To access the anti-tumor activity of ALT-803 administered in combination with gemcitabine
and nab-paclitaxel as measured by objective response rate, overall survival,
progression-free survival, time to progression, and duration of response in patients with
advanced pancreatic cancer.

To Characterize the pharmacokinetic, immunogenicity, and serum cytokine profile of ALT-803
in combination with gemcitabine and nab-paclitaxel in treated patients. To correlate
circulating cell free DNA and circulating tumor DNA with clinical outcomes of the study in
treated patients.

DISEASE CHARACTERISTICS:

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of pancreatic cancer.

- For dose escalation phase (Phase Ib) distant metastatic disease or unresectable
disease and not a candidate for down staging to resection.

- For expansion phase (Phase II) distant metastatic disease only.

- For dose escalation phase (Phase Ib) 0 or 1 prior lines of chemotherapy for advanced
pancreatic cancer. Prior gemcitabine is allowed, however prior nab-paclitaxel is not
allowed.

- For expansion phase (Phase II) no prior therapy for pancreatic cancer is allowed
except for adjuvant therapy as long as it was completed ≥ 6 months prior to study
treatment start

- Have at least one untreated and progressing tumor lesion that can be accurately
measured according to Response Evaluation Criteria in Solid Tumor

- Prior radiation is allowed if the index lesion(s) remains outside of the treatment
field or has progressed since prior treatment. Radiation therapy must have been
completed at least 4 weeks prior to the baseline scan

- Resolved acute effects of any prior therapy to baseline or Grade ≤1

- The Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

- Life expectancy ≥12 weeks

- Glomerular Filtration Rate (GFR) > 45mL (milliliter)/min; Creatinine ≤ 1.5 x ULN
(Upper limit of Normal)

- Platelets ≥100,000/uL (microliter)

- Hemoglobin ≥ 9g/dL

- Absolute Lymphocytes ≥800/uL

- Absolute neutrophil count/absolute granulocyte count ≥1500/uL

- Total bilirubin ≤ 2.0 X ULN, or ≤ 3.0 X ULN (for patients with Gilbert's Syndrome)

- aspartate aminotransferase, alanine aminotransferase ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if
liver metastasis present)

- Normal clinical assessment of pulmonary function

- Negative serum pregnancy test if female and of childbearing potential

- Subjects, both females and males, with reproductive potential must agree to use
effective contraceptive measures for the duration of the study

- Must provide informed consent and HIPPA authorization and agree to comply with all
protocol-specified procedures and follow-up evaluations

Exclusion Criteria:

- No women who are pregnant or nursing

- No known hypersensitivity to gemcitabine or nab-paclitaxel

- No concurrent herbal or unconventional therapy

- No prior therapy with IL-15 or IL-15 analog

- No ongoing toxicity from prior anti-cancer treatment that may interfere with study
treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia
and fatigue must resolve to grade 1 or baseline before administration of the study
treatment.

- No positive Hep C serology or active Hep B infection

- No congestive heart failure < 6 months

- No unstable angina pectoris < 6 months

- No myocardial infarction < 6 months

- No history of ventricular arrhythmias or severe cardiac dysfunction

- No history of uncontrollable supraventricular arrhythmias

- No New York Heart Association Class > II congestive heart failure

- No marked baseline prolongation of QT/QTc interval

- No known autoimmune disease requiring active treatment. Subjects with a condition
requiring systemic treatment with either corticosteroids (>10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days of enrollment.
Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune disease

- No known prior organ allograft or allogeneic transplantation

- No known HIV-positive or AIDS unless patient is on a stable highly active
antiretroviral therapy (HAART) regimen, have CD4 (cluster of differentiation 4)
counts >350, with no detectable viral load on quantitative polymerase chain reaction
test

- No untreated central nervous system metastases, or if treated must be neurologically
stable for at least 2 weeks prior to enrollment

- No corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or
equivalent)

- No psychiatric illness/social situation that would limit compliance

- No other illness that in the opinion of the investigator would exclude the subject
from participating in the study

- No active systemic infection requiring parenteral antibiotic therapy

- No anti-cancer treatment including surgery, radiotherapy, chemotherapy, other
immunotherapy, or investigational therapy within 14 days before treatment start

- No disease requiring systemic immunosuppressive therapy

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease-free for 3 years after
surgical treatment.