AACR: Novel Targeted Therapy Showing Activity in NSCLC and Ovarian Cancers

NEW ORLEANS – A new type of antibody-drug conjugate (ADC) platform may pave the way to help patients with ovarian cancer and non-small cell lung cancer (NSCLC).  

New data presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting are suggesting that the investigational compound known as XMT-1536 may help patients with NaPi2b-expressing tumors. Preclinical data with this immunoconjugate product demonstrated significant anticancer activity in NSCLC and ovarian cancer tumor models (abstract 1194).  

XMT-1536 is a highly potent antisodium-dependent phosphate transport protein 2B (anti-NaPi2b) immunoconjugate, which is being developed by Mersana Therapeutics, Inc. It is comprised of an average of 15 auristatin molecules conjugated to XMT-1535, a novel humanized anti-NaPi2b antibody via the Dolaflexin™ ADC platform.

“We are encouraged by the durable regressions XMT-1536 achieved in non-small cell lung cancer and ovarian cancer tumor models, as well as the excellent tolerability and pharmacokinetics in non-human primate exploratory toxicology studies,” said Donald Bergstrom, MD, PhD, Chief Medical Officer of Mersana, in a news release. “Based on these data, we are advancing XMT-1536 into IND-enabling studies for the treatment of patients with NaPi2b-expressing tumors.”

Researchers evaluated XMT-1536 in nonsquamous NSCLC and nonmucinous ovarian cancer tumor models in which NaPi2b is highly expressed. The study showed that XMT-1536 had significant efficacy in all four patient-derived xenograft models representative of the target patient populations. In three patient-derived models of NSCLC (including KRAS-mutant NSCLC), XMT-1536 induced tumor regressions after 3 weekly doses of 3 mg/kg.

In an ovarian cancer xenograft model, XMT-1536 induced partial tumor regressions after a single dose of 3 mg/kg, and complete tumor regressions after a single dose of 5 mg/kg or 3 weekly doses of 3 mg/kg, according to the researchers. In addition, XMT-1536 was well-tolerated with no evidence of bone marrow toxicity in nonhuman primates at up to seven times the dose associated with tumor regression in the mouse xenograft models.

Mersana Therapeutics has developed Fleximer® immunoconjugate technology. The company contends this technology may be a game-changer and have efficacy against more than one tumor type. Currently, there are two lead compounds based on this technology (XMT-1522 and XMT-1536). Fleximer-based immunoconjugate molecules have been shown to have superior efficacy in targets previously considered not amenable to antibody-drug conjugate approaches, according to the company.

“We look forward to the continued development of this second product candidate in our growing pipeline of Fleximer-based immunoconjugate therapies, as we prepare to enter the clinic with XMT-1522 this year,” said Anna Protopapas, President and Chief Executive Officer of Mersana.