Maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab in FRα-high platinum-sensitive ovarian cancer

Abstract

At first recurrence, platinum-sensitive ovarian cancer (PSOC) is frequently treated with platinum-based chemotherapy doublets plus bevacizumab, then single-agent bevacizumab. Most patients' disease progresses within a year after chemotherapy, emphasizing the need for novel strategies. Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate, comprises a folate receptor alpha (FRα)-binding antibody and tubulin-targeting payload (maytansinoid DM4). In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.

Keywords: GLORIOSA trial; bevacizumab; folate receptor alpha; maintenance therapy; mirvetuximab soravtansine; platinum-sensitive ovarian cancer.

Infographic:

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Figure 1.

Mirvetuximab soravtansine-gynx mechanism of action. Mirvetuximab soravtansine-gynx (MIRV) binds with high affinity to folate receptor alpha (FRα), which is expressed on the tumor cell surface, prompting receptor-mediated internalization of MIRV via antigen-mediated endocytosis. Lysosomal degradation releases the cytotoxic payload, the maytansinoid DM4, that inhibits tubulin polymerization and microtubule assembly. DM4 metabolites then induce potent antimitotic effects that result in cell cycle arrest and apoptosis. The active metabolites may also diffuse into neighboring cells and induce further cell death (termed “bystander killing”). Reproduced without changes from Moore KN, Vergote I, Oaknin A, et al. FORWARD I: a Phase III study of mirvetuximab soravtansine vs. chemotherapy in platinum-resistant ovarian cancer. Future Oncol. 2018;14(17):1669–1678. https://doi.org/10.2217/fon-2017-0646. © 2018 KN Moore. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Figure 2.

GLORIOSA enrollment and trial design. ^aTriplet treatment consists of platinum plus chemotherapy plus bevacizumab for planned six cycles (minimum four and maximum eight cycles), including ≥3 cycles of bevacizumab. ^bFRα-high is defined by FRα positivity of ≥75% of tumor membrane staining at ≥2+ intensity (PS2+). ^cFRα-high participants who desire to be treated and followed while on their run-in triplet therapy must sign a run-in consent as part of the main consent form if they meet other study eligibility criteria as assessed by the investigator. ^dMaintenance treatment must begin ≤12 weeks from last dose of triplet therapy and within 30 days of randomization. Treatment continues until PD, unacceptable toxicity, withdrawal of consent, death or study sponsor termination. ^eAIBW, also known as AdjBW, is calculated as IBW (kg) + 0.4 (actual weight – IBW). IBW for females is calculated as 0.9 × height (cm) – 92. 2L: Second-line; AdjBW: Adjusted body weight; AIBW: Adjusted ideal body weight; CR: Complete response; FRα: Folate receptor α; IBW: Ideal body weight; OS: Overall survival; PARPi: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; PS2+: Positive staining 2+; PSOC: Platinum-sensitive ovarian cancer; Q3W: Three-times per week; SD: Stable disease.