Elahere (mirvetuximab soravtansine-gynx)

P2/3, N=311, Not yet recruiting, Eli Lilly & Co.

To our knowledge, no published studies or case reports have yet documented central nervous system activity of mirvetuximab soravtansine in ovarian cancer. This case highlights a potential new therapeutic role for this agent in patients with ovarian cancer and central nervous system involvement and underscores the need for prospective clinical trials to rigorously assess its central nervous system penetration and efficacy in larger patient cohorts.

Mirvetuximab soravtansine (MIRV), which targets folate receptor-1 (FOLR1), is FDA-approved for platinum-resistant tubo-ovarian cancers with ≥75% moderate/strong staining, and emerging studies show meaningful responses to MIRV combination therapy even at lower FOLR1 expression. FOLR1 met current MIRV treatment criteria in one case, while ten others showed expression ranging from 5% to 70%. Although most tumors did not meet current biomarker thresholds for Trastuzumab or MIRV monotherapy, detectable expression supports exploring anti-HER2 T-Dxd and MIRV combination treatments in selected MA/MLA cases.

We report a 65-year-old patient with heavily pretreated, FRα-positive ovarian cancer who developed therapy-related myelodysplastic syndrome with increased blasts (MDS-IB2, DNMT3A-mutated) during therapy with MIRV in combination with carboplatin having received prior PARPi maintenance therapy. This case demonstrates that MIRV can be safely and effectively administered alongside azacitidine, providing clinically meaningful tumor control without compromising hematologic outcomes. These findings support the concurrent management of ovarian cancer and therapy-related MDS as a viable and underutilized treatment approach in a highly challenging clinical setting.

The results demonstrated significantly higher uptake in CAL51 models compared to MDA-MB-231 models (17.17 ± 2.24%ID/g vs 3.79 ± 1.15%ID/g, P < 0.001), which was further confirmed by subsequent immunohistochemical analysis. In conclusion, 89Zr-DFO-Mirvetuximab holds significant potential for noninvasively identifying TNBC patients with sufficient FRα expression for targeted therapies like Mirvetuximab soravtansine, thereby supporting improved patient stratification and treatment response monitoring.

P3, N=1100, Recruiting, AstraZeneca | N=309 --> 1100

In conclusion, NFTs show an age-dependent FOLR1 expression pattern, which likely reflects hormonal repression of FOLR1 in premenopausal women. NFT tissue from postmenopausal women is appropriate and meets the requirements for the current FOLR1 CDx assay.

This has enabled successful clinical translation of targeted agents: PARP inhibitors for homologous recombination deficient (HRD) ovarian cancer, immune checkpoint inhibitors for mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) endometrial and cervical cancers, and antibody-drug conjugates (ADCs) like mirvetuximab soravtansine and tisotumab vedotin. Equitable access to these advances is imperative to prevent widening health disparities. The field is evolving towards a model of continuous molecular monitoring and adaptive therapy to improve outcomes.

ZW191 demonstrates favourable preclinical efficacy and tolerability. This differentiated profile is supported by initial clinical data, potentially positioning ZW191 to meaningfully improve responses and substantially widen the targetable patient population over standard of care.

MIRV-related ocular alterations are frequent but reversible and clinically manageable. Multimodal imaging combined with functional and refractive assessment provides sensitive markers of corneal epithelial toxicity and supports integrated ophthalmologic monitoring to preserve visual function and maintain oncologic treatment continuity.

P2, N=53, Recruiting, University of Colorado, Denver | Trial completion date: Oct 2028 --> Jan 2031 | Trial primary completion date: Jan 2028 --> Jan 2029

FOLR1 expression in the two cases was weak and below currently used clinical cutoffs for mirvetuximab soravtansine eligibility...Only a subset of anaplastic carcinomas of the ovary express targetable tumor antigens at low levels, suggesting that these may have limited benefit from antibody-drug conjugates. Likewise, due to mismatch repair proficiency and low tumor mutational burden, immunotherapy is unlikely to be effective in this rare disease.