safety of snk01 in subjects with pathologically confirmed metastatic and/or unresectable cancer refractory to conventional therapy

Conditions: Refractory Cancer; Metastatic Cancer; Recurrent Cancer; Unresectable Carcinoma; Solid Tumor, Adult; Advanced Cancer; Advanced Solid Tumor

Summary: the purpose of the study is to evaluate the safety and preliminary efficacy of snk01 (autologous natural killer cell), as a single agent and in combination with avelumab or pembrolizumab, for the treatment of subjects with advanced and/or metastatic refractory cancer that has failed three or more prior lines of conventional standard of care therapy.


Eligibility criteria:
inclusion criteria: * voluntary written informed consent signed by patient, obtained prior to study enrollment. * males and females ages 18 to 75 years, inclusive. * pathologically confirmed diagnosis of refractory cancer that has failed three or more prior lines of conventional standard of care therapy. * diagnosed with any histologically confirmed malignancy whose disease is confirmed to be metastatic and/or unresectable for which standard curative or beneficial treatments are no longer effective. * eastern cooperative oncology group (ecog) performance status \<2. * at least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational). * at least 2 weeks since prior palliative radiotherapy. * adequate bone marrow function: * neutrophils: 2.0-8.0 k/ul * platelet count: 140-440 k/ul * hemoglobin: 10.0-18.0 g/dl * no ongoing transfusion requirements * adequate hepatic function: * serum total bilirubin \< 1.5 x upper limit of normal (uln) * serum albumin ≥ 3.0 g/dl * alanine transaminase (alt) and aspartate transaminase (ast) ≤ 2.5 x uln * international normalized ratio (inr) ≤ 1.5 x uln * adequate renal function with creatinine ≤ 2.0 mg/dl. * negative pregnancy test for women of childbearing potential and use of effective contraception (hormonal or barrier method of birth control) during study. exclusion criteria: * pregnant and/or lactating females. * life expectancy of less than three months. * currently being treated by "biological therapy" as defined by the national cancer institute (example: checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies, treatment vaccines, cytokines, bacillus calmette-guerin (bcg), chimeric antigen receptor t cell therapy (car-t), and natural killer cell therapy). * patients tested positive for hepatitis b and/or c surface antigen. * high fever or any active or unresolved infection, including human immunodeficiency virus (hiv) positive. * autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring immunosuppressive therapy. * prior clinical trial requiring patient to receive an investigational drug within two weeks of enrollment. * congestive heart failure, unstable angina or other underlying cardiac disease; history of thrombosis currently requiring anticoagulation. * mental or psychological illness preventing cooperation with treatment, efficacy evaluations, or unable to understand the informed consent process. * subjects who have undergone prior organ transplantation, including allogeneic stem-cell transplantation. * adult subjects who lack capacity to consent for themselves and for whom consent must be provided by a legally authorized representative. * for snk01+avelumab arm only: subjects with prior hypersensitivity to avelumab or its excipients, including known severe hypersensitivity reactions to monoclonal antibodies (nci ctcae v4.03 grade ≥ 3). * for snk01+avelumab arm only: subjects with a significant immune-mediated adverse event due to a prior checkpoint inhibitor immunotherapy that led to permanent discontinuation of the therapy.

Keywords: natural killer cell nk cell expanded natural killer cell immunotherapy cancer metastatic cancer advanced solid tumor refractory cancer recurrent cancer unresectable carcinoma solid tumor neoplasms