a pilot study of sequential oncos-102, an engineered oncolytic adenovirus expressing gmcsf, and pembrolizumab in patients with advanced or unresectable melanoma progressing after programmed cell death protein 1 (pd1) blockade

Conditions: Advanced or Unresectable Melanoma Progressing After PD1 Blockade

Summary: this is a multi center, phase i pilot study of sequential oncos-102 and pembrolizumab in patients with advanced or unresectable melanoma progressing after pd1 blockade. the primary objective of the study is to determine the safety of sequential treatment with oncos-102 followed by pembrolizumab. the protocol aims to enroll patients into two cohorts: part i: up to 12 patients will receive sequential treatment with oncos-102 followed by pembrolizumab. part ii: up to 12 patients will receive an initial treatment phase with oncos-102 followed by a treatment phase with oncos-102 in combination with pembrolizumab.


Eligibility criteria:
inclusion criteria: * adults 18 years of age or older. * for us sites: histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a food and drug administration (fda) approved anti-pd1 agent, with or without ipilimumab. * for european sites: histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a regulatory approved anti-pd1 agent, with or without ipilimumab. * eastern cooperative oncology group (ecog) performance status 0 to 1. * measurable disease according to recist 1.1. * acceptable coagulation status: international normalised ratio (inr) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal (uln). * completion of local therapy, such as radiation, surgical resection, injectable immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of protocol therapy. * adverse events from previous cancer therapies (excluding alopecia) must have recovered to grade 1 (ctcae, most recent version). stable grade 2 aes such as endocrine conditions are allowed, and other chronic stable aes may be considered on a case by case basis by the principal investigator. * clinical stability of brain metastases for at least 4 weeks prior to first day of study therapy. * acceptable liver and renal functions defined as: * total bilirubin ≤1.5 x uln (does not include patients with gilbert's disease) * aspartate aminotransferase (ast, sgot), alanine aminotransferase (alt, sgpt) ≤3.0 x uln * serum creatinine ≤1.5 x uln * acceptable haematological function defined as (patients can be transfused to meet the haemoglobin entry criteria): * haemoglobin ≥9 g/dl * neutrophils ≥1.5 x 10\^9/l * platelet count ≥75 x 10\^9/l * able to provide valid written informed consent. * all women of childbearing potential must have a negative urine or serum pregnancy test at screening. * for us sites: all patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment and 4 months after the last dose of chemotherapy and pembrolizumab. * for european sites: all patients must agree to use highly effective contraception for at least 6 months (according to the latest country specific smpc) after administration of cpo, up to 4 months after last dose of pembrolizumab, and up to 2 months after last dose of oncos-102, whichever comes last. * for european sites: all women of child-bearing potential must agree to perform pregnancy testing throughout the study starting at baseline, every 3 weeks from day 22 until last dose of study medication (oncos-102 and pembrolizumab) and then every month for at least 6 months. exclusion criteria: * a concomitant medical condition requiring receipt of a therapeutic anticoagulant that in the opinion of the treating physician cannot safely allow for therapeutic injection of oncos-102 and tumor biopsies. local clinical practice can be followed with regard to holding a therapeutic anticoagulant during invasive procedures such as biopsies. * a concomitant medical condition that in the opinion of the treating physician would pose unreasonable additional risk to therapeutic injection of oncos-102. * for us sites: receipt of investigational agents within 28 days prior to first dose of protocol therapy. * for european sites: current participation or participation in a study of an investigational agent within 28 days prior to first dose of protocol therapy. note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. * any symptomatic autoimmune disease (such as lupus, scleroderma, crohn's disease, ulcerative colitis) that requires administration of \>10mg of prednisone equivalent. lower dose steroids for conditions such as hypophysitis are allowed. * any prior severe adverse event attributed to prior anti-pd1 therapy that, in the principal investigator's opinion, would contraindicate pembrolizumab administration such as: * grade 2 or higher pneumonitis * grade 4 ast or alt elevation * grade 3 or higher colitis attributable to pd1 blockade; note that colitis attributable to ipilimumab is not excluded * note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial * known active infection with hepatitis b virus (hbv), hepatitis c virus (hcv), or hiv. cleared hbv/hcv infection is not an exclusion, nor is hiv infection with cluster of differentiations 4 (cd4) counts \>500 and an undetectable viral load. * active bacterial, viral, or fungal infections, requiring systemic therapy apart from anti-viral maintenance therapy for hiv. * history of organ transplant. * patients requiring chronic systemic immunosuppressants, including steroids (prednisone daily equivalent of \>10 mg). * brain metastases that are clinically unstable (e.g. showing unequivocal growth on imaging, requiring radiation therapy, or steroids \>10mg of prednisone equivalent) within 4 weeks of first dose of study drug. * known severe congenital or acquired cellular or humoral immunodeficiency such as common variable immunodeficiency. * for us sites: women who are pregnant or breast-feeding currently or are planning to conceive during or up to 4 months after end of protocol therapy. * for european sites: women who are currently pregnant or breast-feeding or are planning to conceive during or up to 6 months after end of protocol therapy.