Over the past month, the U.S. Food and Drug Administration has granted Fast Track designation to agents designed to treat colorectal and pancreatic cancers, in addition to lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia; accepted a new drug application for a treatment for relapsed or refractory kidney cancer; granted Orphan Drug designation to a novel monoclonal antibody for the treatment of gastric and gastroesophageal junction cancer; and accepted a biologics license application for a novel pegylated interferon for the treatment of polycythemia vera.
Fruquintinib Granted Fast Track Designation for Metastatic Colorectal Cancer
The FDA granted Fast Track designation to fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor (VEGFR) 1/2/3, for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biologic therapy, and, if their disease is RAS wild-type, an anti–epidermal growth factor receptor (EGFR) therapy.
A phase III registration study—FRESCO-2—is being initiated to study fruquintinib in refractory metastatic colorectal cancer in the United States, Europe, and Japan. FRESCO-2 is expected to start enrolling patients in mid-2020. The FDA acknowledged that the totality of the fruquintinib clinical data, including the FRESCO-2 study, if positive; the prior positive phase III FRESCO study demonstrating improvement in overall survival that led to fruquintinib approval for metastatic colorectal cancer in China in 2018; and additional completed and ongoing supporting studies in metastatic colorectal cancer could support a new drug application for the treatment of patients with metastatic colorectal cancer in the third-line setting. The adequacy of the data to support a specific indication will be assessed during the review of a new drug application.
Liposomal Irinotecan Granted Fast Track Designation as Part of a First-Line Combination Treatment for Metastatic Pancreatic Cancer
The FDA granted Fast Track designation for the investigational use of liposomal irinotecan in combination with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin—known as NALIRIFOX—for patients with previously untreated, unresectable, locally advanced and metastatic pancreatic ductal adenocarcinoma.
The final analysis on the efficacy of the combination regimen from a multicenter, open-label phase I/II study will be presented as a late-breaking oral presentation during the virtual ESMO World Congress on Gastrointestinal Cancer next month, and will include data on primary and secondary endpoints. Patient enrollment in the international phase III NAPOLI-3 clinical study has also been initiated. The trial is investigating the safety and efficacy of NALIRIFOX vs gemcitabine/nab-paclitaxel in the first-line setting.
Liposomal irinotecan is approved in the United States and in Europe in combination with 5-FU/LV for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.
CLR 131 Receives Fast Track Designation for Lymphoplasmacytic Lymphoma/Waldenström’s Macroglobulinemia
The FDA granted Fast Track designation for CLR 131 in patients with lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia who received two or more prior treatment regimens. CLR 131 is a small-molecule, cancer-targeting radiotherapeutic phospholipid-drug conjugate designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in the ongoing phase II CLOVER-1 trial in patients with relapsed or refractory multiple myeloma and lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia.
New Drug Application for Tivozanib as a Treatment for Relapsed or Refractory Renal Cell Carcinoma
The FDA accepted for filing a new drug application seeking approval for tivozanib, a next-generation VEGFR tyrosine kinase inhibitor, as a treatment for relapsed or refractory renal cell carcinoma (RCC). The FDA has assigned the application standard review and a Prescription Drug User Fee Act target action date of March 31, 2021. The FDA also indicated that they do not currently plan on convening an Oncologic Drug Advisory Committee) to discuss the application.
The submission is based on the pivotal phase III TIVO-3 study, which compared tivozanib to sorafenib in third- and fourth-line treatment of RCC, including results recently presented at the ASCO20 Virtual Scientific Program (Abstract 5062). The application is also supported by three additional trials, including an active comparator-controlled phase III study, TIVO-1, comparing tivozanib to sorafenib in first line RCC; and two phase II studies: Study 902, the open-label, crossover clinical study of tivozanib for patients whose disease progressed on sorafenib in TIVO-1, and the placebo-controlled Study 201 in first-line RCC. In total, data from over 1,000 clinical trial subjects support the application.
Oprhan Drug Designation for DKN-01 in Gastric and Gastroesophageal Junction Cancer
The FDA granted the Orphan Drug designation to DKN-01 for the treatment of gastric and gastroesophageal junction cancer. DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin signaling. DKK1 has an important role in tumor cell signaling and in mediating an immunosuppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating natural killer ligands on tumor cells.
DKN-01 is currently being evaluated in phase I/II and phase II clinical trials for gastroesophageal, gynecologic, hepatobiliary, and prostate cancers. Site initiation activities are now underway for a combination study of DKN-01 plus tislelizumab in patients with gastric or gastroesophageal junction cancer, with dosing of the first patients expected later in 2020.
Biologics License Application Accepted for Ropeginterferon Alfa-2b in Polythycemia Vera
The FDA recently accepted a biologics license application (BLA) for ropeginterferon alfa-2b (also known as P1101), a novel pegylated interferon intended for the treatment of the rare blood cancer polycythemia vera in the absence of symptomatic splenomegaly. The company expects an agency decision in early 2021.
Ropeginterferon alfa-2b is a structurally novel monopegylated proline interferon designed for administration once every two weeks. The U.S. filing is supported by 24–36-month data from the phase III PROUD/CONTI-PV clinical trial, which demonstrated that the investigational treatment offered hematologic responses and symptom control with good tolerability and low rates of depression observed, with effects on relevant myeloproliferative neoplasm mutations supporting a potential disease-modifying capability.
The findings were shown among patients who received either ropeginterferon alfa-2b (n = 95) or hydroxyurea/best available therapy (n = 74). At 36 months of treatment, patients who received ropeginterferon alfa-2b maintained a complete hematological response longer than those who received hydroxyurea/best available therapy (70.5% vs 51.4%). Response rates increased in the ropeginterferon alfa-2b arm throughout 24 months of treatment and remained constant after 36 months. Further, after 36 months, two-thirds (66.0%) of patients who received ropeginterferon alfa-2b achieved a molecular response, compared with 27% in the hydroxyurea/best available therapy arm. These molecular responses were closely related to complete hematological responses. There were similar rates of adverse events in both arms; the most common (> 10%) treatment-related adverse events included anemia, thrombocytopenia and leukopenia, which occurred more frequently with treatment with hydroxyurea/best available therapy.
