#168 UPLIFT (ENGOT-Ov67/GOG-3048): results from the phase 2 trial of upifitamab rilsodotin (UpRi; XMT-1536), a NaPi2b-directed dolaflexin antibody-drug conjugate (ADC) in platinum-resistant ovarian cancer (PROC)

Introduction/Background

Effective and well-tolerated treatments for PROC remain an unmet medical need; standard of care single agent chemotherapy has limited efficacy, with response rates at ~12%. Upifitamab rilsodotin (UpRi) is a Dolaflexin, high Drug-to-Antibody Ratio ADC targeting NaPi2b, a sodium-dependent phosphate transporter broadly expressed in high-grade serous epithelial ovarian cancer, with limited expression in normal tissues. UPLIFT was a single-arm Ph2 trial evaluating the efficacy and safety of UpRi in PROC.

Methodology

UPLIFT enrolled patients with up to 4 prior lines of therapy; patients were dosed at 36mg/m2 Q4W. Patients enrolled regardless of NaPi2b expression; baseline tumor samples were collected to determine NaPi2b expression retrospectively. Primary endpoint was confirmed ORR in the NaPi2b-positive population. Secondary endpoints included ORR in the overall population, duration of response (DOR), and safety.

Results

268 patients were enrolled, 141 (53%) were determined to be NaPi2b-positive [TPS≥75]. The median prior lines of therapy among all patients was three; 31% received four prior lines of systemic treatment, 53% received at least one prior treatment for PROC. Additionally, 84% of patients received prior bevacizumab, 69% received prior PARPi. Based on data cut (May 31, 2023) investigator assessed confirmed ORR in the NaPi2b-positive population was 15.6% (95% CI, 10, 22.7); median DOR 7.4 months (95% CI, 4.2, NR). In the overall patient population, ORR was 13.1% (95% CI, 9.3, 17.7), DOR 7.4 months (95% CI, 3.6, 10.4). Dose reductions and discontinuations due to TRAE were 25% and 18.7%, respectively. The most frequently reported TRAEs were AST increase (69%), nausea (51.9%), thrombocytopenia/platelet count decrease (49.6%), fatigue (44%), anemia (39.2%) and pyrexia (37.7%). ILD/pneumonitis reported in 9.7% (Gr3 0.7%). Serious treatment emergent bleeding events were observed, including five G5 events.

Conclusion

In this single-arm open label trial, ORR in the NaPi2b-positive and overall population did not show meaningful improvement compared to historical single-agent chemotherapy, though durable responses were observed.

Disclosures

This trial was sponsored by Mersana Therapeutics, Inc.