Dr Crafton on Emerging Therapeutic Targets in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses novel therapeutic targets under investigation in patients with ovarian cancer.

The phase 2 innovaTV 208 trial (NCT03657043) is investigating the tissue factor–directed antibody-drug conjugate (ADC) tisotumab vedotin-tftv (Tivdak) in patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer. This trial is evaluating the ADC in a safety run-in portion, as well as in 3 study groups. Group 1 (part A) will receive the agent once every 3 weeks. Groups 2 (part A) and 3 (part B) will receive the ADC once weekly for 3 weeks on followed by 1 week off. The safety run-in portion of the trial is evaluating the number of patients with dose-limiting toxicities. The primary end point of part B is confirmed overall response rate (ORR). Secondary end points in part B include the number of patients with adverse effects, CA-125 response rate, duration of response (DOR), disease control rate, time to response, progression-free survival (PFS), and overall survival (OS). The final publication of findings from this trial is pending, and these data may influence future clinical practice, Crafton says.

HER2 is another emerging target in ovarian cancer research, having gained prominence as an important prognostic biomarker in several cancers, Crafton explains. For instance, the phase 2 DESTINY-PanTumor02 trial (NCT04482309) is investigating the efficacy and safety of the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-expressing cancers, such as ovarian, endometrial, cervical, biliary tract, bladder, and pancreatic cancers. At a median follow-up of 12.75 months, the ORR in the overall study population was 37.1% (95% CI, 31.3%-43.2%), and responses were observed in all patient cohorts. Furthermore, the median DOR was 11.3 months (95% CI, 9.6-17.8), and the median PFS and OS were 6.9 months (95% CI, 5.6-8.0) and 13.4 months (95% CI, 11.9-15.5), respectively.

HER2-targeted ADCs can produce greater efficacy than monoclonal antibodies, such as trastuzumab (Herceptin), according to Crafton. The development of HER2-directed ADCs will continue in ovarian cancer and other cancers, Crafton concludes.