FOLR1 expression

GTN exhibits frequent expression of several established ADC targets, particularly Nectin4 and FOLR1. These findings provide a molecular rationale for biomarker-driven investigation of ADC-based therapeutic strategies in refractory or recurrent GTN.

High FOLR1 expression identifies a biologically aggressive subset of gastric adenocarcinoma with inferior RFS and independent prognostic value. Its concurrent association with PD-L1 and HER2, together with relative absence in dMMR tumors, supports biomarker-guided strategies that consider FOLR1 alongside HER2 and PD-L1, and provides a rationale to explore FOLR1-targeted therapies in selected patients.

P3, N=530, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

P3, N=520, Recruiting, AbbVie | Trial completion date: Apr 2029 --> May 2032

In this real-world cohort, the addition of bevacizumab to mirvetuximab was associated with improved progression-free survival despite lower FRα expression, supporting potential synergy between these agents. Combination therapy may be considered for appropriately selected patients with FRα-expressing platinum-resistant ovarian cancer.

P1/2, N=37, Recruiting, AbbVie Deutschland GmbH & Co. KG

P1/2, N=29, Recruiting, Incyte Corp.

Lowering FOLR1 expression suppressed tumor growth and boosted paclitaxel sensitivity in mice. FOLR1 plays a significant role in promoting chemoresistance of NPC cells to paclitaxel through NLRP3 signaling.

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.