QUILT-2.001: ALT-803 in Patients With Advanced Pancreatic Cancer in Conjunction With Gemcitabine and Nab-Paclitaxel

Phase Ib/II Study of ALT-803 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Advanced Pancreatic Cancer

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer in 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, 1 or 2

• Life expectancy ≥12 weeks

• Glomerular Filtration Rate (GFR) > 40mL (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.