quilt-2.001: alt-803 in patients with advanced pancreatic cancer in conjunction with gemcitabine and nab-paclitaxel

Conditions: Advanced Pancreatic Cancer

Summary: 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.

Eligibility criteria:
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.

Keywords: pancreas pancreatic cancer advanced pancreatic cancer immunotherapy immunotherapeutic interleukin-15 gemcitabine nab-paclitaxel solid tumor metastatic disease combination immunotherapy