pbf-1129 in patients with nsclc

Conditions: Locally Advanced or Metastatic NSCLC

Summary: phase i clinical trial in eastern cooperative oncology group (ecog) 0-1 patients with locally advanced or metastatic nsclc to evaluate safety and tolerability of the compound pbf-1129, an adenosine a2b receptor antagonist. the phase i dose escalation will be conducted 3+3 method. pharmacokinetic (pk) data will be also obtained.


Eligibility criteria:
inclusion criteria: * histological or cytological diagnosis of metastatic squamous or non-squamous nsclc. * life expectancy greater or equal to 3 months, as determined by the investigator -patients must have progressed on the standard therapy, including platinum based - chemotherapy. patients with epidermal growth factor receptor (egfr), anaplastic lymphoma kinase (alk), or ros-1 mutations must have progressed on standard treatment options including egfr, alk, or ros-1-directed therapies. * no limits to the prior lines of treatment * ecog performance status of 0/1 * measurable disease by recist v1.1 * age greater than 18 years. * adequate bone marrow, renal and hepatic function: * absolute neutrophil count (anc) ≥ 1500 /µl * white blood cell count (wbc) t ≥ 2.5 x 109/l (2500/µl) * lymphocyte count ≥ 0.5 x 109/l (500/µl) * platelet count ≥ 100 x 109/l (100,000/µl) without transfusion * hemoglobin ≥ (9.0 g/dl) - patients may be transfused to meet this criterion. * aspartate aminotransferase ast, alanine aminotransferase (alt), and alkaline phosphatase (alp) ≤ 2.5 x upper limit of normal (uln) * serum bilirubin ≤ 1.5 x uln, with the exception of patients with known gilbert disease: serum bilirubin level ≤ 3 x uln * creatinine clearance \>60 ml/min (calculated using the cockcroft-gault formula) or by 24-hours urine collection * written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations * subject is willing and able to comply with the protocol for the duration of the study exclusion criteria: * participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lives prior to starting on treatment. * symptomatic and/or untreated or actively progressing central nervous system (cns) metastases or leptomeningeal disease. patients with a history of treated cns metastases are eligible, provided that all of the following criteria are met: * the patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment. * the patient has no ongoing requirement for corticosteroids as therapy for cns disease. anti-convulsant therapy at a stable dose is permitted. * serious uncontrolled medical disorder or active infection that would impair the patient's ability to receive study treatment. * concurrent use of other anticancer approved or investigational agents is not allowed. * autoimmune disorder * prior malignancy in past 2 years or as identified in section 7.2 of this protocol * active or prior documented autoimmune disease within the past 2 years. note: patients with vitiligo, grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. * patients receiving systemic steroids ≥ 10mg/day of prednisone or the equivalent * smoking (cigarettes, cigars or pipes) must be discontinued at least 7 days prior to initiating study drug administration; smoking cessation products (transdermal nicotine patches or chewing gum may be used. * pregnancy or breastfeeding, or intention of becoming pregnant during the study. female subjects must either be of non-reproductive potential or have a negative serum pregnancy test result within 14 days prior to initiation of study treatment

Keywords: adenosine receptors checkpoint inhibitors immune system activator