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

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nwEt3X