Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer
| Autor: | Ursula A. Matulonis, Gina Mantia-Smaldone, Cesar M. Castro, Lainie P. Martin, Antonio Gonzalez Martin, Ignace Vergote, Michael J. Birrer, Kathleen N. Moore, Richard T. Penson, Karim Malek, Raquel Bratos, Lucy Gilbert, David M. O'Malley |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Oncology medicine.medical_specialty Antibody-drug conjugate Immunoconjugates Organoplatinum Compounds Bevacizumab medicine.medical_treatment Carcinoma Ovarian Epithelial Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma Humans Folate Receptor 1 Maytansine Progression-free survival Adverse effect Aged Aged 80 and over Ovarian Neoplasms Chemotherapy business.industry Obstetrics and Gynecology Middle Aged medicine.disease Progression-Free Survival 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Monoclonal Female Ovarian cancer business medicine.drug |
| Zdroj: | Gynecologic Oncology. 157:379-385 |
| ISSN: | 0090-8258 |
| Popis: | 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-naive, 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. |
| Databáze: | OpenAIRE |
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