A randomized, open-label, phase II study of anti-NaPi2b antibody-drug conjugate (ADC) lifastuzumab (Lifa) vedotin (DNIB0600A) compared to pegylated liposomal doxorubicin (PLD) in patients (pts) with platinum-resistant ovarian cancer (PROC).

5569 Background: NaPi2b is a transmembrane, sodium-dependent phosphate transporter expressed in ~90% of OC. Lifa, a humanized anti-NaPi2b monoclonal antibody conjugated to the anti-mitotic agent MMAE, was investigated in OC. Methods: The Phase 2 study evaluated the efficacy and safety of lifa at 2.4 mg/kg given intravenously (IV) every 3 weeks (q3w), compared to PLD (40 mg/m2 IV) given q4w, in pts with PROC. The primary endpoint was progression-free survival (PFS) assessed by investigators in intent to treat (ITT) and in NaPi2b-high (IHC 2+/3+) patients. Secondary endpoints included PFS by independent review, safety, and patient-reported outcomes. Tumor NaPi2b expression was assessed by immunohistochemistry (IHC) and quantitative PCR in archival tissue. Results: 95 pts were randomized (47 lifa; 48 PLD). For both arms, the median age was 62, and the median number of prior systemic therapies was 2. 87% of lifa and 85% of PLD pts had no prior PROC therapy. The stratified PFS hazard ratio was 0.78 (95% CI: 0.46-1.31, p = 0.34) with a median PFS of 5.3 months (lifa) vs. 3.1 months (PLD) in the ITT population, and 0.71 (95% CI: 0.40-1.26, p = 0.24) with a median PFS of 5.3 months (lifa) vs. 3.4 months (PLD) in NaPi2b-highpatients. The objective response rate was 34% (95% CI: 22-49%, lifa) vs. 15% (95% CI: 7-28%, PLD) in the ITT population, and 36% (95% CI: 22-52%, lifa) vs.14% (95% CI: 6-27%, PLD) in NaPi 2+/3+ patients per RECIST v1.1. Subgroup analyses demonstrated most benefit in the highest quartile of NaPi2b expressers. Toxicities were: Grade ≥ 3 AEs (46% lifa; 51% PLD), serious AEs (30% lifa; 30% PLD), and AEs leading to discontinuation of drug (9% lifa; 13% PLD). Grade ≥ 2 neuropathy was reported in 5 (11%) lifa patients vs. 2 (4%) receiving PLD. Global HRQOL showed no decline in the lifa arm and a clinically significant decline in the PLD arm over 24 weeks. Conclusions: This is the first randomized study of an MMAE ADC compared to standard of care in PROC. Lifa q3w was well-tolerated with improved ORR and a trend towards increased PFS compared to PLD. These data support using an ADC to target NaPi2b in OC. Clinical trial information: NCT01991210.