Upifitamab rilsodoti, a dolaflexin, high drug-to-antibody ratio antibody-drug conjugate targeting NaPi2b, did not significantly improve objective response rate (ORR) compared to standard single-agent chemotherapy among patients with previously treated platinum-resistant ovarian cancer, regardless of NaPi2b expression. 

The results of the phase 2 UPLIFT trial were first presented by Debra L. Richardson, MD, Stephenson Cancer Center at Oklahoma University, Oklahoma City, at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer. 

“Effective and well-tolerated treatments for platinum-resistant ovarian cancer remain an unmet medical need,” stated Dr Richardson and coauthors. “Standard-of-care single-agent chemotherapy has limited efficacy, with response rates of ~12%.”

In this single-arm, open-label trial, 268 patients with either NaPi2b-positive (n = 141) or -negative platinum-resistant ovarian cancer who underwent ≤4 prior lines of therapy received 36 mg/m² of upifitamab rilsodoti once every 4 weeks. The primary end point was confirmed ORR in the NaPi2b-positive population. Secondary end points included ORR, DOR, and safety in the overall and NaPi2b-positive populations.

At the data cut-off point, investigator-assessed confirmed ORR was 15.6% in the NaPi2b-positive population with a median DOR of 7.4 months. In the overall population, investigator-assessed confirmed ORR was 13.1% with a median DOR of 7.4 months. The most frequently reported treatment-related adverse events of any grade included aspartate aminotransferase increase (69%), nausea (51.9%), fatigue (44%), anemia (39.2%), pyrexia (37.7%), and interstitial lung disease/pneumonitis (9.7%). Some patients experienced grade ≤5 serious treatment-emergent bleeding events. In the NaPi2b-positive population, 25% of patients underwent dose reductions or treatment discontinuation, compared with 18.7% of patients in the overall population.

As Dr Richardson et al concluded, “ORR in the NaPi2b-positive and overall population did not show meaningful improvement compared to historical single-agent chemotherapy, though durable responses were observed.” 

Source: 

Richardson DL, Concin N, Hays JL, et al. UPLIFT (ENGOT-ov67/GOG-3048): Results from the phase II trial of upifitamab rilsodotin, a NaPi2b-directed dolaflexin antibody-drug conjugate in platinum-resistant ovarian cancer. Presented at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer; March 16-March 18, 2024. San Diego, California.