FOLR1 expression

Finally, any-grade ocular adverse events (OAEs) are particularly common in patients during MIRV treatment, arising in 125 (57 %); grade ≥3 in 34 (16 %), most frequently, blurred vision (18 [8 %]), keratopathy (21 [10 %]), cataract (11 [5 %]), and dry eye (8 [4 %]); however, fortunately, over 90 % with OAEs had either full resolution or documented final grade 1 or better. The current review also discusses OAE, based on its high incidence, frequent cause responsible to dose reduction and delaying therapy with impacting 11-35 % of patients and of the most importance, relative unfamiliarity to most gynecological oncologists in the routine clinical practice.

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate (ADC) composed of the DM4 payload conjugated to a folate receptor α (FRα)-targeting antibody via the cleavable sulfo-SPDB linker. The MIRV Phase 3 registrational trial (MIRASOL) showed superiority of MIRV vs. chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) in patients with high (≥ 75%) FRα-expression PROC, showing an objective response rate of 42% versus 16%, a median progression-free survival of 5.6 versus 4.0 months, and an overall survival of 16.5 versus 12.8 months. Here, we briefly review MIRV mechanism of action, pharmacokinetics, pharmacodynamics, and key clinical efficacy and safety data.

P2/3, N=860, Recruiting, Daiichi Sankyo | Trial completion date: Dec 2029 --> Apr 2030

Additionally, we conducted a systematic investigation into the associations between FRα expression and clinicopathological characteristics, highlighting its capacity to reflect FRα heterogeneity, maintain stability in post-chemotherapy FRα expression across various tumor types, and achieve robust performance in excision/resection samples. These findings underscore the value of standardizing FRα testing to improve patient selection for FRα-targeted MIRV therapies in China.

P1, N=216, Completed, Bio-Thera Solutions | Recruiting --> Completed | Trial primary completion date: Dec 2024 --> Dec 2025

Purinergic inhibitory post-junctional motor responses were greatly attenuated in the GI tracts of crenolanib treated animals compared to vehicle treated controls in response to electric field evoked nerve stimulation. These data provide evidence for a functional role of PDGFRα+ cells in inhibitory neuroeffector motor responses throughout the gastrointestinal tract.

The findings of this study indicate that approved radionuclide therapies targeting SSTR2 or PSMA are unlikely to be suitable for treating EOC. In contrast, the frequent and high expression of FRα in tumor cells and FAP in tumor-associated stromal cells suggests that FRα- and FAP-targeted radiopharmaceuticals hold promise for the treatment of advanced-stage EOC.

FZEC showed promising antitumor activity, and the observed adverse events were generally manageable, with the exception of ILD, in patients with PROC.

Approximately half of the ovarian cancer patients in this multicenter Polish cohort demonstrated FOLR1 positivity. Although this prevalence is lower than that reported in high-grade serous carcinoma cohorts, it likely reflects histological heterogeneity and methodological differences between studies. These findings provide the first population-based evidence from Poland and support the implementation of FOLR1 testing to guide access to mirvetuximab soravtansine. Further research integrating clinical and molecular data is warranted to validate these results and assess implications for cost-effectiveness and patient outcomes.

FOLR1 is overexpressed in a large percentage of low-grade serous ovarian cancers. Mirvetuximab soravtansine may represent a novel treatment option for low-grade serous ovarian cancer patients progressing after standard treatment modalities. Clinical trials with mirvetuximab soravtansine in FOLR1-positive low-grade serous ovarian cancers are warranted.

P1/2, N=764, Recruiting, Genmab | N=569 --> 764

Complete resection and advanced stage were suggested as prognostic factors in UCS. FRα and Trop-2 are increasingly recognized as therapeutic targets and their elevated expression levels in the epithelial component of UCS are promising, although not associated with prognosis in this cohort.