Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared to pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study

Abstract

Background

Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent anti-mitotic agent, monomethyl auristatin E (MMAE), which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug-conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients.

Patients and Methods

Platinum-resistant OC patients were randomized to receive LIFA (2.4 mg/kg, intravenously, every 3 weeks [Q3W]), or pegylated liposomal doxorubicin (PLD) (40 mg/m², intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary endpoint was progression-free survival (PFS) in intent to treat (ITT) and NaPi2b-high patients.

Results

Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 (95% CI, 0.46–1.31; p=0.34) with a median PFS of 5.3 vs. 3.1 months (LIFA vs. PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40–1.26; p=0.24) with a median PFS of 5.3 vs. 3.4 months (LIFA vs. PLD arm, respectively) in NaPi2b-high patients. The objective response rate (ORR) was 34% (95% CI, 22–49%, LIFA) vs. 15% (95% CI, 7–28%, PLD) in the ITT population (p=0.03), and 36% (95% CI, 22–52%, LIFA) vs.14% (95% CI, 6–27%, PLD) in NaPi2b-high patients (p=0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA vs. 2 (4%) PLD patients had grade ≥ 2 neuropathy.

Conclusion

Lifastuzumab vedotin Q3W was well-tolerated and improved ORR with a modest, non-statistically significant improvement of PFS compared to PLD in platinum-resistant OC. While the response rate for the MMAE-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADC's in OC.

Clinical trials.gov

NCT01991210