TY - JOUR
T1 - A phase I/II study of rovalpituzumab tesirine in delta-like 3—expressing advanced solid tumors
AU - Mansfield, Aaron S.
AU - Hong, David S.
AU - Hann, Christine L.
AU - Farago, Anna F.
AU - Beltran, Himisha
AU - Waqar, Saiama N.
AU - Hendifar, Andrew E.
AU - Anthony, Lowell B.
AU - Taylor, Matthew H.
AU - Bryce, Alan H.
AU - Tagawa, Scott T.
AU - Lewis, Karl
AU - Niu, Jiaxin
AU - Chung, Christine H.
AU - Cleary, James M.
AU - Rossi, Michael
AU - Ludwig, Carrianne
AU - Valenzuela, Ricardo
AU - Luo, Yan
AU - Aggarwal, Rahul
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Delta-like protein 3 (DLL3) is highly expressed in solid tumors, including neuroendocrine carcinomas/neuroendocrine tumors (NEC/NET). Rovalpituzumab tesirine (Rova-T) is a DLL3-targeting antibody-drug conjugate. Patients with NECs and other advanced DLL3-expressing tumors were enrolled in this phase I/II study (NCT02709889). The primary endpoint was safety. Two hundred patients were enrolled: 101 with NEC/NET (large-cell NEC, gastroenteropancreatic NEC, neuroendocrine prostate cancer, and other NEC/NET) and 99 with other solid tumors (melanoma, medullary thyroid cancer [MTC], glioblastoma, and other). The recommended phase II dose (RP2D) was 0.3 mg/kg every 6 weeks (q6w) for two cycles. At the RP2D, grade 3/4 adverse events included anemia (17%), thrombocytopenia (15%), and elevated aspartate aminotransferase (8%). Responses were confirmed in 15/145 patients (10%) treated at 0.3 mg/kg, including 9/69 patients (13%) with NEC/NET. Rova-T at 0.3 mg/kg q6w had manageable toxicity, with antitumor activity observed in patients with NEC/NET, melanoma, MTC, and glioblastoma.
AB - Delta-like protein 3 (DLL3) is highly expressed in solid tumors, including neuroendocrine carcinomas/neuroendocrine tumors (NEC/NET). Rovalpituzumab tesirine (Rova-T) is a DLL3-targeting antibody-drug conjugate. Patients with NECs and other advanced DLL3-expressing tumors were enrolled in this phase I/II study (NCT02709889). The primary endpoint was safety. Two hundred patients were enrolled: 101 with NEC/NET (large-cell NEC, gastroenteropancreatic NEC, neuroendocrine prostate cancer, and other NEC/NET) and 99 with other solid tumors (melanoma, medullary thyroid cancer [MTC], glioblastoma, and other). The recommended phase II dose (RP2D) was 0.3 mg/kg every 6 weeks (q6w) for two cycles. At the RP2D, grade 3/4 adverse events included anemia (17%), thrombocytopenia (15%), and elevated aspartate aminotransferase (8%). Responses were confirmed in 15/145 patients (10%) treated at 0.3 mg/kg, including 9/69 patients (13%) with NEC/NET. Rova-T at 0.3 mg/kg q6w had manageable toxicity, with antitumor activity observed in patients with NEC/NET, melanoma, MTC, and glioblastoma.
UR - http://www.scopus.com/inward/record.url?scp=85116954441&partnerID=8YFLogxK
U2 - 10.1038/s41698-021-00214-y
DO - 10.1038/s41698-021-00214-y
M3 - Article
C2 - 34354225
AN - SCOPUS:85116954441
SN - 2397-768X
VL - 5
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 74
ER -