Nektar Therapeutics has announced an expanded Phase 2 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 2 study in advanced colorectal cancer.
In addition, NKTR-102 will be evaluated in Phase 2 trials in two new indications: platinum-refractory ovarian cancer and advanced breast cancer that is refractory to anthracycline and/or taxane-based therapies. These studies are expected to commence in the second half of 2008.
Recent data presented at the 2008 American Society of Clinical Oncologists (ASCO) Annual Meeting shows colorectal cancer (CRC) patients with tumors 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% 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 is 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, M.D., 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 tumors in this patient population," Haller said.
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 tumor 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.