Elahere (mirvetuximab soravtansine-gynx)

Mirvetuximab soravtansine-gynx, an FRα-targeting ADC, has been approved by the FDA and EMA for the treatment of FRα-positive, platinum-resistant ovarian cancer... These findings highlight the critical importance of standardized, validated assays for FRα detection to ensure accurate patient selection for targeted therapies. The study emphasizes the need for further optimization of alternative antibodies before clinical implementation.

P3, N=1080, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

MIRV demonstrates significant efficacy and an acceptable safety profile in the treatment of recurrent ovarian cancer. Its use in platinum-resistant ovarian cancer with high FRα expression represents a particularly promising Therapeutic approach. Furthermore, the combination of MIRV and bevacizumab shows substantial potential for improving outcomes in patients with platinum-resistant disease.

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate approved for the treatment of adult patients with folate receptor 1 (FRα; FOLR1) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens...Our study highlights several factors contributing to heterogeneity in FOLR1 reporting. Future studies are needed to better understand the impact of FOLR1 heterogeneity on patient response to therapy.

P2, N=320, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P2, N=140, Not yet recruiting, AbbVie | Trial completion date: Oct 2029 --> Feb 2030 | Initiation date: Aug 2025 --> Nov 2025

P2, N=53, Recruiting, University of Colorado, Denver | Trial completion date: Dec 2027 --> Oct 2028 | Trial primary completion date: Apr 2026 --> Jan 2028

Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects.

For solid cancers, these comprise the antibody-drug-conjugate Mirvetuximab Soravtansine for platinum-resistant ovarian cancer, the monoclonal antibody Zolbetuximab for Claudin-18.2 positive gastric adenocarcinoma and the checkpoint inhibitor Tislelizumab for esophageal squamous cell carcinoma. For the treatment of relapsed or refractory hematologic B cell malignancies, the use of bispecific T cell engaging antibodies like the BCMA-CD3 targeting Teclistamab and CD20-CD3 targeting Glofitamab were approved by the EMA recently.Combinatorial approaches of conventional chemotherapy and checkpoint inhibitors for the treatment of cholangiocarcinoma, urothelial carcinoma and endometrial carcinoma received recent approval.A CD38 antibody-based bridging therapy for the treatment of newly diagnosed multiple myeloma and the Glofitamab-based approach in combination with Gemcitabine and Oxaliplatin for relapsed DLBCL are the latest additions for hematologic malignancies after promising clinical trials.The first T cell products for the treatment of solid cancers using either tumor-infiltrating lymphocytes or TCR-engineered peripheral blood T cells were approved by the FDA in 2024, for the treatment of advanced melanoma (Lifileucel) and synovial sarcoma (Afamitresgene autoleucel). To further expand the success of T cell products to solid tumors, promising preclinical studies suggest solutions to main obstacles, such as modular CAR T cells, targeting of two antigens simultaneously or generation of cytokine-secreting 4th generation CAR T cells.

P3, N=1100, Not yet recruiting, AstraZeneca

P3, N=1080, Not yet recruiting, Eli Lilly and Company

AZD5335 is a promising next-generation ADC capable of targeting ovarian cancers with both high and low FRα expression. AZD5335 demonstrates efficacy in overcoming Elahere-resistance and supports combined treatment strategies.