ADCs offer the opportunity for a more effective and personalized treatment approach for gynecologic cancer patients. Side effects must be closely monitored, and preventive measures must be followed to maximize benefit and minimize toxicity. A better understanding of the role of target proteins as biomarkers to predict response to ADCs will be critical for successful clinical implementation of ADCs and further research in this area is necessary.

P2, N=200, Not yet recruiting, Daiichi Sankyo

P2/3, N=650, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

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.

P2/3, N=650, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P1, N=180, Recruiting, OnCusp Therapeutics, Inc. | Not yet recruiting --> Recruiting

P1, N=180, Not yet recruiting, OnCusp Therapeutics, Inc.

R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting.

P2/3, N=650, Not yet recruiting, Daiichi Sankyo, Inc.

DXd demonstrated cytotoxicity in all PDC models, regardless of CDH6 expression, whereas control ADC and anti-CDH6 naked antibody showed no growth inhibitory effects. Conclusions CDH6 is an attractive target for EOC and R-DXd is a promising agent for the treatment of CDH6-expressing EOC.

Results As of 03 March 2023, 42 patients with OVC had received R-DXd at 4.8 (n = 7), 6.4 (n = 20), and 8.0 (n = 15) mg/kg: 40 (95%) had platinum-resistant disease, 29 (69%) had received prior bevacizumab, and 26 (62%) had received prior PARP inhibitors. Eleven of 21 GCIG-evaluable patients (52%) had a CA-125 response. Conclusions In heavily pretreated OVC patients without CDH6 preselection, R-DXd demonstrated acceptable safety and encouraging preliminary efficacy, which supports further clinical development in OVC.

P1, N=140, Recruiting, Daiichi Sankyo, Inc. | Trial completion date: Jul 2023 --> Oct 2024 | Trial primary completion date: May 2023 --> Oct 2024