NKTR-214 Shows Activity in Phase I RCC Study

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Nektar Therapeutics presented positive phase I data for Nektar’s lead immuno-oncology agent, NKTR-214, in patients with renal cell carcinoma.

The data were presented at ASCO GU 2017.

NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer cells.

“NKTR-214 resulted in dramatic increases in tumor-infiltrating lymphocytes and also demonstrated encouraging anti-tumor activity, with 40% of RCC patients experiencing tumor reductions, including one patient with a partial response,” said Mary Tagliaferri, vice president, clinical development, at Nektar. “We know that high TIL levels are correlated with clinical response and longer survival in patients treated with checkpoint inhibitor therapies and can be the best predictor of response. NKTR-214’s unique mechanism, favorable safety profile and clinical activity support our combination trials of NKTR-214 with existing checkpoint inhibitors, such as nivolumab and atezolizumab, but also with other I-O mechanisms in development.”

Clinical benefit and safety data were presented on 15 patients from the trial with renal cell carcinoma who were treated with single-agent NKTR-214:

  • 6/15 (40%) patients with RCC had radiographic reductions in tumor size per RECIST 1.1 on NKTR-214, including: o 3 patients who had progressed on 1 prior tyrosine kinase inhibitor (TKI) and had also progressed on 1 prior checkpoint therapy o 3 patients who had progressed on 1 prior tyrosine kinase inhibitor (TKI) and were checkpoint therapy naïve, including 1 patient who experienced an unconfirmed partial response (uPR)

  • NKTR-214 continues to demonstrate a favorable safety and tolerability profile with convenient, outpatient q3w or q2w administration in all patients evaluable for safety to-date. Immune pheno-typing was conducted and biomarkers of immune activation were measured in patients with evaluable tumor biopsies and blood samples.Treatment with NKTR-214 produced a robust elevation in immune cell frequency and activation, including:

  • Increase in total lymphocytes and newly proliferating (Ki67+) CD4+ T cells, CD8+ T cells, and NK cells, with increases greater than 50-fold observed • Increase in CD8+ T cells of up to 10-fold in the tumor micro-environment in patients with evaluable tumor biopsies (pre-dose and post-dose at week 3)

  • Increase in expression of cell-surface PD-1 on T cell subsets of up to 2-fold in the tumor micro-environment Nektar and Bristol-Myers Squibb are collaborating to develop NKTR-214 as a potential combination treatment regimen with Bristol-Myers Squibb’s Opdivo (nivolumab) in five tumor types and eight potential indications.

The phase I/II clinical program will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients.

The initial dose-escalation trial is underway with Opdivo (nivolumab) and NKTR-214 in the indications of first-line melanoma, second-line RCC checkpoint therapy-naïve, and second-line non-small cell lung cancer checkpoint therapy-naïve.