David M O'Malley1, Ursula A Matulonis2, Michael J Birrer3, Cesar M Castro4, Lucy Gilbert5, Ignace Vergote6, Lainie P Martin7, Gina M Mantia-Smaldone8, Antonio González Martin9, Raquel Bratos10, Richard T Penson11, Karim Malek12, Kathleen N Moore13. 1. The Ohio State University, Columbus, OH, United States. Electronic address: David.O'Malley@osumc.edu. 2. Dana Farber Cancer Institute, Boston, MA, United States. Electronic address: Ursula_Matulonis@dfci.harvard.edu. 3. University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, United States. Electronic address: mbirrer@uab.edu. 4. Massachusetts General Hospital, Boston, MA, United States. Electronic address: Castro.Cesar@mgh.harvard.edu. 5. McGill University Health Centre, Montreal, QC, Canada. Electronic address: lucy.gilbert@mcgill.ca. 6. Leuven Cancer Institute, Leuven, Belgium. Electronic address: ignace.vergote@uzleuven.be. 7. University of Pennsylvania, Philadelphia, PA, United States. Electronic address: Lainie.Martin@uphs.upenn.edu. 8. Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address: Gina.Mantia-Smaldone@fccc.edu. 9. Clinica Universidad de Navarra, Madrid, Spain. Electronic address: agonzalezma@unav.es. 10. MD Anderson Cancer Center Madrid, Madrid, Spain. Electronic address: rbratosl@hospiten.com. 11. Massachusetts General Hospital, Boston, MA, United States. Electronic address: Penson.Richard@mgh.harvard.edu. 12. ImmunoGen, Inc., Waltham, MA, United States. Electronic address: karim.malek@immunogen.com. 13. Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Sarah Cannon Research Institute, Nashville, TN, United States. Electronic address: Kathleen-Moore@ouhsc.edu.
Abstract
PURPOSE: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, platinum-resistant ovarian cancer. METHODS: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. RESULTS: Sixty-six patients, with a median of 3 prior lines of therapy (range, 1-8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (≤grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxicities. Six cases of pneumonitis (9%; all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naïve, less heavily pretreated (1-2 prior lines), and whose tumors exhibited medium/high FRα expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). CONCLUSION: The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with platinum-resistant, recurrent ovarian cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations.
PURPOSE: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, platinum-resistant ovarian cancer. METHODS:Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. RESULTS: Sixty-six patients, with a median of 3 prior lines of therapy (range, 1-8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (≤grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxicities. Six cases of pneumonitis (9%; all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naïve, less heavily pretreated (1-2 prior lines), and whose tumors exhibited medium/high FRα expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). CONCLUSION: The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with platinum-resistant, recurrent ovarian cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations.
Authors: Jung-Min Lee; Christina M Annunziata; John L Hays; Liang Cao; Peter Choyke; Minshu Yu; Daniel An; Ismail Baris Turkbey; Lori M Minasian; Seth M Steinberg; Helen Chen; John Wright; Elise C Kohn Journal: Gynecol Oncol Date: 2020-08-01 Impact factor: 5.482
Authors: Asim V Farooq; Simona Degli Esposti; Rakesh Popat; Praneetha Thulasi; Sagar Lonial; Ajay K Nooka; Andrzej Jakubowiak; Douglas Sborov; Brian E Zaugg; Ashraf Z Badros; Bennie H Jeng; Natalie S Callander; Joanna Opalinska; January Baron; Trisha Piontek; Julie Byrne; Ira Gupta; Kathryn Colby Journal: Ophthalmol Ther Date: 2020-07-25