Nektar Therapeutics presented data at the American Association for Cancer Research (AACR) 100th Annual Meeting demonstrating that NKTR-105, a novel PEGylated form of docetaxel, has superior anti-tumour activity, as well as greater and sustained exposure in plasma and tumour tissue, over docetaxel in preclinical models.
In a comparative study of NKTR-105 and docetaxel, NKTR-105 treatment significantly delayed tumour growth as compared to docetaxel (122% v. 48%), which was associated with greater and sustained tumour exposure to docetaxel after NKTR-105 administration. Treatment with NKTR-105 increased docetaxel concentrations in tumors (0.4 to 4-fold higher) and resulted in an improved time-concentration profile (two-fold greater) as compared to docetaxel in a non-small cell lung (H460) mouse xenograft model.
"The encouraging antitumor activity and unique pharmacokinetic profile of NKTR-105 in these data support our ongoing Phase 1 study in patients with refractory solid cancers," said Randall Moreadith, senior vice president, Drug Development and chief development officer. "We believe NKTR-105 has the potential to offer improved efficacy as well as improved safety and tolerability due to its prolonged half-life and increased uptake by tumour tissue relative to docetaxel. We are excited about the drug's potential to significantly expand therapeutic options for oncologists and patients."
In previous preclinical studies, NKTR-105 demonstrated superior anti-tumour activity with no neutropenia in multiple tumour models, indicating that NKTR-105 may enable sustained therapeutic levels of docetaxel without the myelosuppression that is a dose-limiting toxicity for this widely-used cancer therapy.
NKTR-105 is currently being evaluated in a phase-1 clinical trial in cancer patients. The phase-1 study will assess the safety, pharmacokinetics and anti-tumour activity of NKTR-105 in approximately 30 patients with refractory solid tumours who have failed all prior available therapies. In the current trial of NKTR-105, the compound has required no pre-treatment with corticosteroids and shown no evidence of neutropenia in patients to date.
NKTR-105 is a novel form of docetaxel that was developed using Nektar's advanced polymer technology platform.
Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms.