P2, N=50, Terminated, Bristol-Myers Squibb | Trial completion date: Feb 2026 --> Aug 2024 | Recruiting --> Terminated; Business objectives have changed

P3, N=110, Not yet recruiting, AbbVie

P1/2, N=24, Recruiting, Sutro Biopharma, Inc. | Not yet recruiting --> Recruiting

P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2028 --> May 2027 | Trial primary completion date: Aug 2025 --> Jun 2024

P1, N=58, Recruiting, Sutro Biopharma, Inc. | Active, not recruiting --> Recruiting

P1/2, N=24, Not yet recruiting, Sutro Biopharma, Inc.

P1/2, N=142, Recruiting, Eisai Inc. | Trial completion date: Mar 2025 --> Oct 2024 | Trial primary completion date: Mar 2025 --> Oct 2024

As demonstrated among 682 participants, the safety profile of MIRV is well tolerated and consists primarily of low-grade gastrointestinal, fatigue, headache, peripheral neuropathy, and resolvable ocular adverse events.

P2, N=136, Active, not recruiting, AGO Research GmbH | Recruiting --> Active, not recruiting

P1/2, N=170, Not yet recruiting, Bio-Thera Solutions | Initiation date: Sep 2024 --> Jan 2025

P1/2, N=396, Recruiting, AstraZeneca | N=150 --> 396

Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy. Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.

97.5% had prior taxanes, 81% prior poly (ADP-ribose) polymerase inhibitors (PARPi) [74.7% of whom progressed while on PARPi], 64.6% prior bevacizumab, 98.8% had 2+ prior lines of therapy, and BRCA status was 27.8% positive, 72.2% negative. MIRV demonstrated notable efficacy in this heavily pretreated PSOC population, including among those who may have PARPi resistance. MIRV continues to demonstrate a differentiated safety profile consisting primarily of low-grade neurosensory, GI, and resolvable ocular AEs. These data position MIRV to become a novel treatment option for patients in ≥3L PSOC with FRα positive expression.

Introduction Mirvetuximab soravtansine-gynx (MIRV) is an antibody-drug conjugate that binds to folate receptor alpha and delivers a microtubule inhibitor payload...Median PFS did not significantly differ based on number of prior treatment lines (for 1-3 versus >3 lines, P = 0.3) or prior PARP inhibitor ( P = 0.9) or bevacizumab ( P = 0.4) use...Conclusion/Implications MIRV confers meaningful PFS benefit for a subset of individuals. Biomarkers of response and resistance are urgently needed to optimize patient selection for treatment.

P3, N=530, Not yet recruiting, Genmab

The trough concentration of MIRV correlated with efficacy whereas the AUC of MIRV was associated with major AEs. The ER relationships supported the selected therapeutic dose regimen.

P=N/A, N=50, Recruiting, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital Hainan Hospital; Hangzhou ZhongMei Huadong Pharmaceutical Co., Ltd.

P1, N=145, Recruiting, Zymeworks BC Inc. | Not yet recruiting --> Recruiting

P2/3, N=600, Recruiting, Sutro Biopharma, Inc. | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Sep 2025 --> Aug 2027

P2, N=100, Recruiting, ImmunoGen, Inc. | Not yet recruiting --> Recruiting

P2, N=43, Recruiting, Sutro Biopharma, Inc. | Not yet recruiting --> Recruiting

P2, N=50, Recruiting, Alessandro Santin

P2, N=43, Not yet recruiting, Sutro Biopharma, Inc.

P1, N=145, Not yet recruiting, Zymeworks BC Inc.

P1/2, N=170, Not yet recruiting, Bio-Thera Solutions

P1, N=227, Recruiting, ImmunoGen, Inc. | Trial primary completion date: Jun 2024 --> Dec 2024

P3, N=453, Active, not recruiting, ImmunoGen, Inc. | Trial completion date: Apr 2024 --> Aug 2024

P1, N=136, Completed, Sutro Biopharma, Inc. | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Jun 2024

In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.

In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments...Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC)...Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

Here, we report updated nonanalytical results based on a median follow-up of 16.7 months. 453 PROC pts with high FRα expression (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) with 1-3 prior therapies were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or ICC: paclitaxel (PAC), pegylated liposomal doxorubicin (PLD), or topotecan (Topo). With a median follow-up of 16.7 months, MIRV demonstrated improved efficacy vs ICC in pts with PROC. The efficacy data, along with the well-characterized safety profile, supports MIRV as the standard of care for pts with FRα positive PROC. Clinical Trial Information: NCT04209855.

97.5% had prior taxanes, 81% prior poly (ADP-ribose) polymerase inhibitors (PARPi) [74.7% of whom progressed while on PARPi], 64.6% prior bevacizumab, 98.8% had 2+ prior lines of therapy, and BRCA status was 27.8% positive, 72.2% negative. MIRV demonstrated clinically meaningful antitumor activity and favorable tolerability in patients with FRα-high PSOC. The efficacy and safety data support the use of MIRV in PSOC patients with ≥ 2 prior platinum-containing regimens or platinum allergy. Clinical Trial: NCT05041257.

Mirvetuximab soravtansine (MIRV), an FRα-targeting antibody-drug conjugate, is active in high-grade serous epithelial ovarian cancer (HGSOC)... FRα was highest in HGSOC and was associated with advanced stage and BRCA status. Sample age, anatomical site, and PFI did not affect FRα expression, suggesting that any sample is suitable for determining FRα status. Variability was observed in cores from the same specimen, which appeared to be driven by tumour heterogeneity versus biological changes.

Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup.

Mirvetuximab soravtansine is an antifolate receptor alpha monoclonal antibody, with an approved FOLR1-2.1 immunohistochemical biomarker...Significant differences in FOLR1 staining were noted between histotypes, age of the specimen, type of case tested, and site of disease tested. Further testing is needed to help determine the best tissue to be utilized for this new biomarker.

P1, N=160, Active, not recruiting, Sutro Biopharma, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Aug 2024 --> Nov 2024

P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | N=35 --> 18 | Trial completion date: Oct 2026 --> Aug 2028 | Trial primary completion date: Oct 2024 --> Aug 2025

P1, N=58, Active, not recruiting, Sutro Biopharma, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

These results support the clinically meaningful efficacy of mirvetuximab soravtansine-gynx in FRα-expressing platinum-resistant ovarian cancer, irrespective of prior treatment or sequence.

P1/2, N=25, Recruiting, Takeda | Not yet recruiting --> Recruiting

However, identified gaps, including limited diversity in patient populations, sparse quality of life data, and the need for long-term safety information, indicate areas for future research. Exploration of additional biomarkers predicting mirvetuximab soravtansine responsiveness is essential for personalized treatment.

P1, N=220, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting