Mersana Therapeutics announced the initiation of a phase I b extension study with its lead cancer product, XMT-1001, a novel DNA topoisomerase I inhibitor based on the company’s Fleximer polymer conjugate platform, in second-line gastric cancer and second-/third-line non-small cell lung cancer (NSCLC).

The study will be carried out in 10 clinical centers in the US. The phase I b follows the successful completion of a 74-patient phase I clinical trial, which demonstrated high and prolonged plasma levels of XMT-1001 active release products and a safety profile free of the toxicities normally associated with topoisomerase 1 inhibitors, such as haemorrhagic cystitis and diarrhoea.

Additionally, XMT-1001 showed promising evidence of clinical activity, including tumor shrinkage and prolonged stable disease, in a heavily pre-treated patient population.

“Our recently completed phase I study has confirmed the potential efficacy and safety advantages of the unique design of our lead Fleximer conjugate, XMT-1001,” said Nick Bacopoulos, PhD, CEO of Mersana. “We believe we are now able to fully explore the broad anti-tumor potential of XMT-1001 and are excited to initiate recruitment in our phase I b programme.”

“Our clinical experience with XMT-1001 to date suggests that it can be safely given up to doses limited by its mechanism, and thus may be useful in maximizing the therapeutic potential of its class. The potential benefit of this agent in second-line gastric cancer and in second-/third-line non-small cell lung cancer, areas of great medical need, is well worth investigating,” said Edward A. Sausville, MD, PhD, Professor of Medicine and Associate Director for Clinical Research, University of Maryland Greenebaum Cancer Center and a principal investigator in the phase I b study.

XMT-1001 is Mersana’s most advanced Fleximer-based product candidate. It utilizes a proprietary, dual-release mechanism to liberate a novel, active camptothecin analogue, which can be further converted into camptothecin, a DNA topoisomerase I inhibitor. In preclinical studies, XMT-1001 was significantly more efficacious and better tolerated than either camptothecin or  irinotecan in models of human cancer, showing extended plasma half-life and high, prolonged concentrations in tumour tissue.

The phase I trial was an open label, dose escalation study of XMT-1001 administered as an IV infusion once every three weeks in patients with advanced solid tumours. The study has determined the Maximum Tolerated Dose (MTD) to be 113 mg/m2 camptothecin equivalents and assessed the safety and pharmacokinetics of XMT-1001.

Mersana is transforming oncology product development by creating new anti-cancer agents through application of its Fleximer polymer conjugate platform. Fleximer is a novel, biodegradable and bio-inert polymer that can be chemically linked to drugs, including small chemical entities, peptides and biologics. Fleximer-based compounds can be individually designed to optimize the therapeutic performance of drugs by modulating such properties as circulation time and site of release, while significantly improving safety.

Mersana, a privately held, venture-backed company, utilizes its proprietary polymer conjugate platform to transform existing and experimental anti-cancer agents into new, patentable drugs with superior pharmaceutical properties.