Nektar Therapeutics today reported positive Phase 1 data for its lead oncology product candidate, NKTR-102 (PEG-irinotecan), as well as positive preclinical data for NKTR-105 (PEG-docetaxel). The two product candidates leverage Nektar's small molecule PEGylation platform.

The data were presented at the 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland, and highlighted the significant anti-tumor activity and superior pharmacokinetic profile of NKTR-102 on one hand and the significantly greater anti-tumor activity of NKTR-105 as compared to docetaxel in colorectal (LoVo and LS174T) and non-small cell lung (H460) on the other hand.

The NKTR-102 (PEGylated irinotecan) dose-escalation trial, evaluated the safety, pharmacokinetics and anti-tumor activity of its monotherapy in 57 patients with advanced solid tumors who had failed prior treatments or had no standard treatment available to them. The 57 patients were placed into one of three dose schedules and received 90-minute infusions of NKTR-102 weekly for three weeks with the fourth week off.  Tumor responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

During the study, 13 reported relevant anti-tumor activity with seven confirming partial responses ranging from 40% reduction to 58% reduction in tumor size. Six other patients showed minor responses (tumor regression by more than 15 percent but less than 30 percent per RECIST, or demonstrated significant cancer biomarker reduction).

Patients in the study had previously failed all prior established treatment regimens and most showed progressive disease despite three or more previous regimens. All partial responses were observed following the first or second course of treatment, highlighting the value of an oncolytic with an extended half-life and sustained delivery of the active metabolite.

Observed responses to the study included tumor regression, other anti-tumor activity or prolonged disease stabilization in a broad spectrum of cancer types, including triple-negative breast, ovarian, cervical, bladder, non-small cell lung cancer, small cell lung cancer, adrenocortical, esophageal, maxillary sinus and Hodgkins lymphoma.

Nektar expects to present complete results from this ongoing Phase I trial at additional scientific forums later this year, as well as the initiation of Phase II studies to evaluate NKTR-102 in these tumor types in the fourth quarter of 2008.

Further, the company presented positive preclinical data demonstrating anti-tumor activity through NKTR-105 (PEG-docetaxel), showing significantly greater anti-tumor activity than docetaxel in colorectal and non-small cell lung mouse xenograft models of human tumors. Partial tumor regressions were observed in LoVo and LS174T for NKTR-105, while no regressions were observed for docetaxel. The percent of tumor growth delay for NKTR-105 at maximum tolerated doses ranged between 1.6 and 2.5 times greater than the other medications.

The company plans to file an Investigational New Drug Application (IND) for NKTR-105 by end of 2008 to initiate a Phase 1 clinical study.

Nektar Advanced PEGylation Technology works to enhance the properties of small and large molecules by increasing drug circulation time, improving pharmacokinetics, decreasing immunogenicity and dosing frequency, increasing bioavailability and improving drug solubility and stability. PEGylation Technology has been used the development of several approved and marketed products including: Neulasta(R) (pegfilgrastim) for the treatment of neutropenia, Macugen(R) (pegatanib sodium) for the treatment of wet age-related macular degeneration, PEGASYS(R) (pegylated interferon α 2a) for the treatment of hepatitis C and Somavert(R) (pegvisomant) for the treatment of acromegaly.

Source: Nektar Therapeutics