お知らせ • Jul 16
Celcuity Announces FDA Approval of REVTORPYK™ (Gedatolisib) for the Treatment of HR+/HER2-, PIK3CA Wild-Type Locally Advanced or Metastatic Breast Cancer
Celcuity announced that the U.S. Food and Drug Administration approved REVTORPYK (gedatolisib) for the treatment of patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. REVTORPYK is the only inhibitor of class I PI3K isoforms (a, ß, d, ?) and mTOR complexes mTORC1 and mTORC2 to receive FDA approval. HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers. Among this breast cancer subtype, approximately 60% have PIK3CA wild-type disease. The approval of REVTORPYK is based on positive clinical results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial, an open-label, global, randomized clinical trial evaluating the efficacy and safety of REVTORPYK plus fulvestrant, with or without palbociclib, for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 therapy and an aromatase inhibitor. In the VIKTORIA-1 trial, median progression free survival (PFS) with the REVTORPYK triplet (REVTORPYK plus palbociclib and fulvestrant) was 9.3 months versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months (HR=0.24; 95% CI: 0.17-0.35; p<0.0001). REVTORPYK is a kinase inhibitor of class I PI3K isoforms (a, ß, d, ?) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT. REVTORPYK is in development for the first-line treatment of HR+/HER2- locally advanced or metastatic breast cancer and for the second-line treatment of metastatic castration resistant prostate cancer. REVTORPYK (gedatolisib) is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Stomatitis occurred in 72% of patients treated with REVTORPYK with fulvestrant and palbociclib, including Grade 3 events in 22% of patients. Stomatitis occurred in 58% of patients treated with REVTORPYK with fulvestrant, including Grade 3 events in 12% of patients. Rash occurred in 30% of patients treated with REVTORPYK in combination with fulvestrant and palbociclib, including Grade 3 events in 6% of patients. Rash occurred in 40% of patients treated with REVTORPYK with fulvestrant, including 5% of patients with Grade 3 events. Increased fasting glucose occurred in 46% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib (Grade 3: 0.9%) and in 57% of patients receiving REVTORPYK in combination with fulvestrant (Grade 3: 1.8%). The safety of REVTORPYK has not been established in patients with Type 1 or uncontrolled Type 2 diabetes mellitus. REVTORPYK can cause fetal harm when administered to a pregnant woman. Advise women not to breastfeed during treatment with REVTORPYK and for 2 weeks after the last dose. REVTORPYK in Combination with Fulvestrant and Palbociclib: The most common (=20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant and palbociclib were decreased white blood cells, decreased neutrophils, decreased hemoglobin, decreased lymphocytes, stomatitis, nausea, decreased platelets, increased fasting glucose, fatigue, vomiting, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), musculoskeletal pain, decreased sodium, and increased eosinophils. REVTORPYK in Combination with Fulvestrant: The most common (=20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant were stomatitis, glucose increased, eosinophils increased, hemoglobin decreased, nausea, rash, ALT increased, fatigue, musculoskeletal pain, lymphocytes decreased, vomiting, AST increased, pruritus, and diarrhea. Advise women not to breastfeed during treatment with REVTORPYK and for 2 weeks after the last dose. Advise females and males of reproductive potential that REVTORPYK may impair fertility.