Nektar Therapeutics has presented 18-month data on its NKTR-214-Opdivo combination in first-line melanoma. The phase 1/2 results show the efficacy seen at 12 months has persisted, providing early evidence to support Nektar’s belief NKTR-214 can drive durable, deepening responses.
NKTR-214, also known as bempeg, initially underwhelmed when combined with Bristol-Myers Squibb’s checkpoint inhibitor in treatment-naïve melanoma patients, delivering overall and complete response rates (ORR/CRR) of 50% and 11%, respectively. Since then, the steady uptick of the CRR has improved perceptions of the drug and its prospects of succeeding in a pivotal trial.
Saturday, Nektar shared another six months of data from the phase 1/2 trial. The ORR and CRR are still at 53% and 34%, respectively, meaning the hoped-for additional complete responses failed to materialize.
With the ORR and CRR unchanged, the most notable aspects of the update relate to durability. At the time of the 12-month follow-up earlier this year, Nektar said 16 of the 20 patients with responses had ongoing responses. In the new 18-month update, Nektar said 17 of the 20 patients had ongoing responses. The trial is yet to reach median duration of response or median progression-free survival (PFS).
Nektar has seen a second case of grade 3 or 4 treatment-related acute kidney injury since the 12-month update, bringing the rate of the adverse event up to 5%. A fifth patient discontinued due to a treatment-related adverse event.
Jonathan Zalevsky, senior vice president and chief research and development officer at Nektar, thinks the safety and efficacy back up the company’s belief in the combination.
“The 18-month follow-up data presentation for the Stage IV melanoma patients in our PIVOT-02 study reinforces the promise of bempeg and nivo to work synergistically to achieve a deepening of response over time, while maintaining a favorable safety and tolerability profile,” Zalevsky said in a statement.
Nektar’s trial design means it is hard to tell whether NKTR-214 will live up to the promise seen by Zalevsky. In the absence of a comparator arm, it is unclear whether NKTR-214 is adding to the responses triggered by Opdivo.
Advocates of NKTR-214 can point to monotherapy data on Opdivo generated in other trials to argue that the Nektar drug is having a positive effect. However, the immuno-oncology sector has already seen such apparent positive effects in single-arm trials can be illusory, most notably when a phase 3 study showed adding Incyte’s epacadostat to Merck’s Keytruda had no effect on PFS. Epacadostat looked as promising as NKTR-214 by some metrics in an earlier single-arm study.
Working with its partner Bristol-Myers, Nektar is now enrolling 764 melanoma patients in a clinical trial that will show whether NKTR-214 adds to the efficacy achieved by Opdivo. Participants are taking either NKTR-214 and Opdivo or Bristol-Myers’ checkpoint inhibitor as a monotherapy.
Nektar's shares were up around 10% on the news Monday morning.