NKTR-214 with Opdivo Earns FDA’s Breakthrough Therapy Designation for Advanced Melanoma

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation for a combination of the potential therapy NKTR-214 with Opdivo (nivolumab) for untreated melanoma patients with either metastatic disease or who are unable to undergo surgery.

A global Phase 3 clinical trial (NCT03635983) comparing the effectiveness and safety of add-on NKTR-214 to Opdivo alone in first-line treatment of advanced melanoma patients is currently enrolling. More information on contacts, open locations and those yet to open can be found here.

NKTR-214, or bempegaldesleukin, is Nektar Therapeutics’ lead immuno-oncology candidate. It works by promoting the activation and proliferation of a subset of immune T-cells and natural killer (NK) cells, both capable of eliminating cancer cells.

Specifically, NKTR-214 binds to CD122, a subunit of the IL-2 receptor on immune T- and NK cells, which boosts the levels of these cells and their anti-tumor response. The investigational medication also increases the levels of the PD-1 protein on T-cells and PD-L1 on cancer cells, suggesting that it may boost the effectiveness of immune checkpoint inhibitors, such as Bristol-Myers Squibb’s Opdivo. (Of note, Opdivo blocks the interaction of PD-1 with PD-L1, a mechanism used by tumors to evade immune attack.)

Breakthrough therapy designation is intended to speed the development of therapies that show early evidence of offering substantial improvement over existing alternatives. The FDA’s decision was based on 12-month follow-up results of the ongoing PIVOT-02 Phase 1/2 clinical trial (NCT02983045), specifically the group of patients with metastatic melanoma who received both NKTR-214 and Opdivo.

In this subset, 53% of the patients showed response to treatment, including participants whose tumor surroundings were deemed the least favorable —  without PD-L1 and with low levels of T-cells.

Those findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. PIVOT-02 also is assessing treatment with NKTR-214, Opdivo, and Yervoy (ipilimumab, also developed by Bristol-Myers Squibb), and cancer types other than melanoma. Those include renal cell carcinoma, non-small cell lung cancer, bladder cancer, and triple negative breast cancer.

“In collaboration with our partner Bristol-Myers Squibb, we plan to work closely with FDA as we continue to advance our development program of bempegaldesleukin in combination with nivolumab [Opdivo],” Stephen Doberstein, senior vice president, research and development and chief R&D officer at Nektar, said in a press release.

“Our teams are encouraged by the deepening of responses we observed in … PIVOT-02,” said Doberstein said, adding that the companies plan to present updated findings at a future medical meeting.

Nektar and Bristol-Myers Squibb have been working together in the development of NKTR-214 since February 2018.

Recently, a lawsuit was filed in federal court in California on behalf of all investors who purchased Nektar securities between Feb. 15 and Aug. 8, 2019.

According to the complaint, the company did not comply with current good manufacturing practices, leading to meaningful differences across NKTR-214 batches. As a result, PIVOT-02 results have differed based on NKTR-214 batch and do not support clinical benefit. Taken together, these issues mean that Nektar has made statements about its business, operations, and prospects that were misleading and/or lacked a reasonable basis, the complaint alleges.

Such allegations were based on Nektar’s report on Aug. 8 that a manufacturing issue caused two NKTR-214 batches (used in 22 patients) to differ from the other 20 and resulted in reduced clinical benefit, yet similar safety findings, compared to the other batches used in PIVOT-02. According to the company, no material from these two batches is currently being used and a control strategy to limit such variances has been developed and submitted to the FDA.

A conference call held on that day is available for replay through Sept. 9on Nektar’s website.

More details about the lawsuit can be found here.