Nektar Therapeutics has announced an expanded phase II development plan for NKTR-102 (PEG-irinotecan). The company will target newly-characterized colorectal cancer patients with K-Ras mutated gene status in its phase II study in advanced colorectal cancer.

In addition, NKTR-102 will be evaluated in phase II trials in two new indications: platinum-refractory ovarian cancer and advanced breast cancer that is refractory to anthracycline and taxane-based therapies. These studies are expected to commence in the second half of 2008.

Recent data were presented at the 2008 American Society of Clinical Oncologists (ASCO) Annual Meeting shows colorectal cancer (CRC) patients with tumours that have K-Ras oncogene mutations (K-Ras mutant types) do not respond to EGFR-inhibitors, such as cetuximab. It is estimated that up to 45 per cent of colorectal cancer cases have this mutated K-Ras gene.

To target this newly- characterized K-Ras mutant patient population, Nektar will initiate a prospective study to evaluate the efficacy of NKTR-102 monotherapy in these patients. The primary endpoint of this randomized trial will be a clinically meaningful improvement in progression-free survival as compared to standard irinotecan monotherapy.

"With these recent clinical studies on K-Ras, there are no longer a clear standard of care for the second-line treatment of advanced colorectal cancer in patients with the K-Ras gene mutation," said Daniel Haller, MD, Professor of Medicine at the Abramson Cancer Center at the University of Pennsylvania. "This novel oncolytic, NKTR-102, could offer an alternative and promising approach for tumours in this patient population".

The company also announced new trials for NKTR-102 in breast and ovarian cancer. These studies will be open-label, single-arm studies to evaluate the overall response rate (ORR) of NKTR-102 monotherapy in each tumour setting. The studies will implement a minimax design, known as the Simon design, which was first proposed by Dr Richard Simon of the National Cancer Institute in 1989. The two-stage design is routinely used in the evaluation of oncolytics.

"The promise of NKTR-102 and our small molecule PEGylation platform is capturing a great deal of attention among oncologists and clinical investigators," said Howard W. Robin, Nektar President and CEO. "We've seen significant and repeat anti-tumour activity in our phase I study with NKTR-102. Our expanded phase II clinical development plan will potentially accelerate our understanding and development of this novel therapy in multiple cancer types".

Nektar is developing NKTR-102, a PEGylated form of irinotecan, which was invented by Nektar using its world-leading small molecule PEGylation technology platform. The product is currently in a phase IIa study to evaluate NKTR-102 in combination with cetuximab.