FOLR1 expression

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.

Compound juvenile Pdgfrα-CreER;Ext1f/f and Fgf18-CreER;Ext1f/f mice were injected with tamoxifen and monitored for tumor development over time...Analyses also showed that the developing osteochondromas in the Pdgfrα;Ext1 mutants displayed strong expression of cartilage proteins and abundant pSMAD1 and pSMAD2 proteins that mediate pro-chondrogenic BMP/TGFβ signals. The data provide new evidence that perichondrium progenitors, and more specifically inner layer cells delineated by Pdgfrα expression, initiate osteochondroma formation, being redirected into an ectopic chondrogenic program by Ext1 loss and deficiency of its vital function.

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.

P2/3, N=860, Recruiting, Daiichi Sankyo | N=344 --> 860

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.

P1/2, N=0, Withdrawn, Centre Leon Berard | N=87 --> 0 | Not yet recruiting --> Withdrawn

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.