Dr Richardson on the Safety of Upifitamab Rilsodotin in Platinum-Resistant Ovarian Cancer

Debra L. Richardson, MD, FACS, FACOG, associate professor, chief, Section of Gynecologic Oncology and Oklahoma, TSET Phase I Program, Stephenson Cancer Center, The University of Oklahoma (OU) College of Medicine, OU Health, discusses the safety profile of upifitamab rilsodotin (UpRi; XMT-1536) in the phase 1/2 UPLIFT trial (NCT03319628) of patients with ovarian cancer, and highlights other promising research presented during the 2024 SGO Annual Meeting on Women’s Cancer.

Findings from the UPLIFT trial findings offered insights into the efficacy and safety profile of upifitamab rilsodotin in platinum-resistant recurrent ovarian cancer. The agent produced an overall response rate (ORR) of 15.6% (95% CI, 10.0%-22.7%) in those with NaPi2b-positive disease (n = 141) fell short of meeting the predefined threshold for the trial’s primary end point, and the lower confidence interval limit did not exclude 12%. Based on these data, the development of upifitamab rilsodotin was discontinued since it did not meet its primary objective in this trial, she emphasizes.

Regarding safety, upifitamab rilsodotin displayed a manageable adverse effect (AE) profile, and was primarily associated with grade 1/2 toxicities, Richardson states. Elevations in aspartate aminotransferase, nausea, fatigue, anemia, and decreased platelet count were noted alongside an anticipated occurrence of pneumonitis in approximately 9.6% of patients, she elucidates. However, the emergence of grade 5 bleeding events, 4 of which were deemed treatment-related, underscores the importance of vigilant monitoring and management of potential complications associated with this therapy, Richardson reports.

In addition to the UPLIFT trial, noteworthy presentations at the 2024 SGO Annual Meeting included an overview of raludotatug deruxtecan (DS-6000) in platinum-resistant ovarian cancer, which is slated for evaluation in the upcoming phase 2/3 REJOICE-Ovarian01 trial (NCT06161025), Richardson continues. The phase 2 RAMP 201 trial (NCT04625270) exploring the RAF, MEK, and FAK inhibitor avutometinib (VS-6766) in low-grade serous ovarian cancer also piqued interest, along with a presentation of updated survival data from the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796), she says. These presentations collectively offer a comprehensive glimpse into the evolving treatment paradigm in ovarian cancer, highlighting novel therapeutic avenues and ongoing efforts to improve patient outcomes, Richardson concludes.