Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: PURPOSE: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC). PATIENTS AND METHODS: Following a run-in phase I study to assess ARB safety, prrHGOC patients with centrally confirmed MSLN positive expression were randomized to ARB or PB (wP 80mg/m2 with Bev 10mg/kg biweekly). Patients were stratified by platinum resistance/refractory and prior Bev. The primary endpoint was progression-free survival (PFS), secondary endpoints were overall response rate (ORR), safety, and blood-based angiome biomarker assessment. A futility analysis was planned after 35 PFS events. RESULTS: The combination of Bev (10mg/kg) biweekly with AR (2.2mg/kg) weekly was well tolerated. Regarding phase II results, mesothelin positivity was 88% and 57 pts were randomized (28 ARB, 29 PB). 42% pts received prior Bev and 23% were platinum refractory. At futility analysis, the median PFS was 5.3 and 12.7 months for ARB and PB respectively (p=0.03, HR= 2.02 [1.06-3.86]). ORR was 21% with ARB and 65% with PB. The most common treatment-related grade ≥ 3 adverse events were anemia (18%) with ARB, and neutropenia (24%) with PB. Higher baseline levels of circulating IL-6 were associated with worse PFS, and its levels decreased with PB treatment. CONCLUSION: Our study stopped at interim analysis highlighting the benefit of PB in prrHGOC as standard of care.
Source: UNC Libraries
DOI: 10.17615/ayp4-sm26
Authors: Jewell, Andrea, Bowering, Valerie, Alqaisi, Husam A, Madariaga, Ainhoa, Oza, Amit M, Duska, Linda R, Wang, Lisa, Lee, Crystal, Chen, Li, McKee, Tawyna, Dhani, Neesha C, Lheureux, Stephanie, Nixon, Andrew B, Girda, Eugenia, Cohn, David E, Crispens, Marta A, Zamboni, William, Speers, Vanessa, Winer, Ira Seth, Malaguti, Matthew, Poothullil, Andrew, Chern, Jing-Yi, Brady, John C, Corr, Bradley R, Moscow, Jeffrey A, Bedard, Philippe L, Wong, Horace, O'Connor, Claire, Grant, Robert C
Institution: University of North Carolina at Chapel Hill
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204646399
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