NKTR-102 Successful In Patients With Refractory Solid Tumors

Armen Hareyan's picture

Nektar Therapeutics announced initial results today from a Phase 1 study of NKTR- 102, PEGylated irinotecan. The data shows significant anti-tumor activity in patients with refractory solid tumors. The study also demonstrates that Nektar's small molecule PEGylation technology produced an increase in SN38 exposure that was up to six-fold higher than the exposure previously reported with irinotecan at equivalent doses. SN38, a topoisomerase I inhibitor, is the active metabolite of irinotecan.

The ASCO abstract reports interim data on 27 of 32 patients in the first of three dose schedules from the Phase 1 trial.(1) Results for the first schedule (weekly x3 q4 weeks) found anti-tumor activity in 7 out of the total 32 patients evaluable for efficacy. Partial responses were confirmed in three patients, or 10% (greater than 30% tumor regression per RECIST), and other evidence of anti-tumor activity was confirmed in four patients, or 12% (tumor regression by more than 15% but less than 30% per RECIST, or significant biomarker evidence).

"This significant anti-tumor activity in a number of patients whose tumors have progressed on prior therapies makes NKTR-102 one of the most promising cancer drugs I have ever studied," said Daniel D. Von Hoff, M.D., lead Phase 1 investigator for NKTR-102, Physician-in-Chief at the Translational Genomics Research Institute and Chief Medical Officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare.

Nektar's proprietary PEGylation technology can enhance the properties of therapeutic agents by increasing drug circulation time, improving pharmacokinetics, decreasing immunogenicity and dosing frequency, increasing bioavailability and improving drug solubility and stability.

"The impressive Phase 1 results with NKTR-102 represent a major advancement for our small molecule PEGylation platform," said Howard W. Robin, President and CEO of Nektar. "Using our proprietary technology, Nektar is the first company to create a PEGylated small molecule with a unique pharmacokinetic profile that has demonstrated therapeutic activity in patients. This pioneering success with NKTR-102 validates our platform and opens the door to a wide range of potential small molecule opportunities. "


Clinical Trial Summary

In the Phase 1 dose-escalation trial, the safety, pharmacokinetics and anti-tumor activity of NKTR-102 monotherapy was evaluated in patients with refractory solid tumors. Patients received 90-minute infusions of NKTR-102 (PEGylated irinotecan) repeated as follows: weekly for three weeks with the fourth week off; every two weeks; or every three weeks. Tumor responses are being evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

In the first dose schedule (weekly x3 q4 weeks), NKTR-102 was administered to a total of 32 patients with advanced solid tumors who had failed prior treatments or had no standard treatment available to them. Doses ranged from 58 mg/m2 to 230 mg/m2. Tumor regression, anti-tumor activity or prolonged disease stabilization was observed in a number of cancer types, including non- small cell lung cancer, ovarian, small cell lung cancer, cervical, adrenocortical, esophageal, and Hodgkin's lymphoma.

Results from the second and third dose schedules of this Phase 1 trial will be presented by featured speaker, Dr. Daniel D. Von Hoff, at an investor event on June 2, 2008. The Webcast event will begin at 6 pm Central time and will occur during the American Society of Clinical Oncology (ASCO) 2008 Annual Meeting in Chicago, Illinois. Nektar will also present its Phase 2 clinical development plan for NKTR-102.

Side effects in the first dose schedule were diarrhea and neutropenia and were identified as manageable toxicities, with diarrhea being the dose-limiting toxicity associated with administration of NKTR-102. The recommended Phase 2 dose (RP2D) was 115 mg/m2. No Grade 4 or Grade 5 toxicities were observed with administration of NKTR-102.

The Phase 1 trial, sponsored by Nektar Therapeutics, includes clinical sites at Translational Generational Clinical Research Services at Scottsdale Healthcare and the Louisville Oncology Clinical Research Program. The company also expects to present results from this trial at additional scientific forums later this year.