FOLR1 expression

P2/3, N=108, Not yet recruiting, Incyte Corp.

FZEC demonstrated modest antitumor activity, and observed AEs were generally manageable in patients with heavily pretreated NSCLC. NCT03386942.

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.

Endometrial tumors with FOLR1 overexpression had a significantly higher rate of TP53 mutations (P=0.013), while all endometrial tumors with PTEN alterations were negative for FOLR1 (P=0.037). Overall, FOLR1 overexpression was associated with poor prognostic factors, such as advanced clinical stage, increased recurrence rate, higher pathologic T and N stage, poor histologic grade, larger tumor size, lymphovascular invasion, uterine serosa involvement, and shorter progression-free survival.

Our findings demonstrate that HER3 is a robust prognostic biomarker in HGSC and support a biologically relevant HER3-FOLR1 interaction contributing to tumor aggressiveness. These results provide a translational rationale for combined biomarker assessment and for the development of HER3- and FOLR1-targeted therapeutic strategies, particularly antibody-drug conjugates, for HGSC.

We report a population of high FOLR1-expressing tumor-associated macrophages (CD163 + FOLR1 + ), suggesting potential on-target, off-tumor immune editing by MIRV. A composite biomarker score derived in this cohort correlates with objective response to MIRV and pembrolizumab.

The high expression levels of FRα in ovarian cancer but absence in the bone marrow of human tissue samples infer therapeutic and safety benefits of using FRα-selective folate radioconjugates. Measures to reduce renal retention of 6S-5-MTHF radioconjugates may, however, still be necessary.

Recently, the antibody-drug conjugate mirvetuximab soravtansine has been approved for treatment of advanced platinum-resistant high-grade serous carcinoma (HGSC)...In conclusion, these results confirm that FRα expression in HGSC and LGSC reaches similar values compared to published data, and is present in a minority of endometrial serous carcinomas. In other ovarian and endometrial tumors examined, FRα expression is absent or rare.

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