A Phase II, multi-center, open label study of NIR178 in combination with PDR001 in patients with selected advanced solid tumors and non-Hodgkin lymphoma (CNIR178X2201)
Johns Hopkins Kimmel Cancer Center in Baltimore
The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.
Patients must be 18 years old or over with ECOG performance status 0-2 as determined by study team. Patients must have histologically documented advanced or metastatic disease and meet protocol specific disease criteria in order to be eligible for either Part 1: histologically confirmed renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite stable (MSS) colon cancer, triple negative breast cancer (TNBC) or melanoma OR Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. (Protocol Expansion into Part 3 limited to NSCLC plus one solid tumor type) Patients (other than those with DLBCL) must previously have received at least 1 and no more than 3 prior lines of therapy for their disease and meet the study specific stipulations for prior therapy. Patients with DLBCL should be limited to those with no available therapies of proven clinical benefit and should have had prior auto-HSCT or determined to be ineligible for auto-HSCT. Patients must have measurable disease as defined by protocol AND must have a site of disease amenable to biopsy AND be willing to undergo a new tumor biopsy at screening, and again during therapy on this study. Patients must not have received prior immunotherapy. (Part 3 will allow previous immunotherapy for NSCLC only) Prior brain metastasis is allowed if patient is stable, asymptomatic and does not require symptoms management/concurrent treatment. NO chemotherapy, immunotherapy or cancer directed therapy within 2 to 6 weeks (depending on therapy) prior to starting trial. NO immunosuppressive medications within 28 days of first dose. NO surgeries within past 14 days. No ongoing intercurrent illness or social situations that would limit compliance with study requirements. NO history of autoimmune disease within last 2 years. NO history of inflammatory bowel disease, interstitial lung disease or non-infectious pneumonitis, primary immunodeficiency, allogeneic organ or stem cell transplant, leptomeningeal carcinomatosis or TB. NO ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinson’s) may be considered on a case by case basis. Smoking nicotine products must be discontinued within 7 days of first dose, smoking cessation products may be used. Other inclusion/exclusion criteria per protocol specifics.
Treatment will be administered on an outpatient basis. NIR 178 will be taken orally either BID continuously (Part 1) OR as randomized by protocol (Part 2 and 3). PDR001 to be given IV over 30 minutes once every 28 days.
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