SUO poster presentation, Thursday, Dec 1, 2016
Jeffery Lin BS1, Nir Kleinmann MD2, Gregory Wirth MD3, Surena Matin MD4, Ofer Nativ MD5, Gil Mayer MD5, Fred Witjes MD6, Asaf Shvero MD2, Karim Chamie MD7, Allen Pantuck MD8, Angie Smith MD9, Mark Schoenberg MD10,11, Nadav Malchi11, Gil Hakim BSc11, Michal Jeshurun−Gutshtat MD11, Ifat Klein PhD11, Helen Kopelen CCRC, CCRP1 and Seth Lerner MD, FACS1
1Baylor College of Medicine, Houston, TX; 2Chaim Sheba Medical Center, Tel−Ha’Shomer, Israel; 3Geneva University Hospital, Geneve, Switzerland; 4MD Anderson Cancer Center, Houston, Texas; 5Benai−Zion Medical Center, Haifa, Israel; 6University of Nijmegen, Mijmegen, Netherlands; 7University of California, Los Angeles, Los Angeles, CA; 8University of California Los Angeles, Los Angeles, CA; 9University of North Carolina, Chapel Hill, NC; 10The Montefiore Medical Center and The Albert Einstein College of Medicine, Bronx, New York; 11UroGen, Pharma Ltd., Ra’anana, Israel
Introduction and objectives: There is a large unmet need for novel drug delivery systems and effective therapy for UTUC, especially for patients with chronic kidney disease and anatomic solitary kidneys. A temperature sensitive water−soluble gel formulation of Mitomycin C (MitoGel) has demonstrated increased time of drug delivery (4 to 6 hrs) and safety in the pelvicalyceal system of swine and human bladders. This report examines the efficacy and safety of MitoGel used for UTUC on a compassionate use basis.
Methods: Compassionate use approval was obtained on an individual patient basis from the respective regulatory authorities and IRBs. Eighteen patients have been approved for treatment to date from 11 institutions in 4 countries in Israel, Europe and the US. Treatment included 6 weekly instillations of MitoGel instilled via ureteral catheter or percutaneous nephrostomy, and 2 patients received maintenance treatment following a complete response (CR). MitoGel volume ranged from 5−20cc and concentration was 2−6 mg/cc. Adverse events were recorded throughout treatment. Ureteroscopy was performed 2−6 weeks following treatment completion for response determination.
Results: Median age of the cohort was 73.5 yrs, with 13 males. Fourteen patients had low−grade (LG) tumor, 2 high−grade (HG), and 2 indeterminate grade. Eight patients had a solitary kidney and 13 had non−resectable tumor. Thirteen (72.2%) completed treatment − 7 patients had a CR (38.9%; 53.8% of those who completed tx), 3 had partial response (16.7%; 23.1%), and 2 patients had no response (11.1%; 15.4%). Three patients could not complete treatment due to adverse events (pyelonephritis, acute renal failure, pancytopenia, and unstable cardiac condition), 1 patient was diagnosed with a second non−urothelial cancer during treatment, and 1 patient died prior to the third instillation due to suspected pulmonary embolus, determined to be unrelated to treatment with MitoGel. A total of 67 adverse events were recorded with 6 events related to MitoGel and serious (requiring intervention), and 21 events related to MitoGel and not serious. CR (7) and PR (3) were observed in 10 of 11 evaluable patients completing treatment for LG tumors.
Conclusion: This compassionate use program of MitoGel for chemoablation of UTUC demonstrates proof of concept for treatment of low−grade tumors. A single arm Phase III multi−center registration trial to treat patients with low−grade renal pelvis tumors is planned for Fall, 2016.