First ever randomized study comparing an ADC to standard of care in platinum-resistant ovarian cance


In a study sponsored by Genentech titled Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (LIFA) compared to pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer in a randomized, open-label, phase II study, the ADC was able to significantly shrink or regress tumor growth (i.e. objective response rate). Unfortunately, LIFA did not significantly improve relative survival. LIFA targets NaPi2b, which is a sodium-dependent phosphate transporter that is expressed at a level of 2+/3+ in 90% of ovarian tumors. It is unclear how ubiquitously expressed or at what level NaPi2b is on normal tissues. Nonetheless, previous clinical studies showed encouraging toxicity results for LIFA. 95 patients in total were tested (47 for LIFA and 48 for PLD). The key findings were that patients who expressed 3+ NaPi2b had greater tumor regression and improved survival. One potential mechanism for resistance was thought to be NaPi2b down-regulation. Its currently unknown what Genentechs future plans for LIFA will be. I'll keep you posted!