ASCO: Complete response rate in Nektar melanoma trial hits 34%

Nektar Therapeutics
Bristol-Myers Squibb’s Opdivo-Yervoy combination ultimately achieved a complete response rate of 21% in a phase 3 trial. (Nektar Therapeutics)

Nektar Therapeutics has posted updated data on its NKTR-214-Opdivo cocktail in first-line melanoma. The data features four more complete responses, bringing the rate up 10 percentage points to 34%.

Around this time last year, Nektar left the 2018 American Society of Clinical Oncology (ASCO) annual meeting bruised after the 50% response rate in its NKTR-214-Opdivo trial underwhelmed. Months later, the next update at the Society for Immunotherapy of Cancer (SITC) 2018 meeting did little better, with the bump up to 53% failing to convince many people that the combination is a winner.

Throughout that time, Nektar pointed to the rising rate of complete responses, up from 11% at ASCO to 24% at SITC, to argue that the effect of the drug was deepening over time, offering encouragement as it and Bristol-Myers Squibb embarked on a sweeping R&D program.

Now, Nektar has arrived at this year’s ASCO with data that strengthen its complete response story. Of the 38 melanoma patients who received the combination as a first-line therapy, 13 have experienced complete responses. That results in a complete response rate of 34%.

The overall response rate remains stuck at 53%, a figure in line with that achieved by the Opdivo-Yervoy combination, but there are now signs that NKTR-214 may have an edge in complete responses. After four years of follow-up, Bristol-Myers’ Opdivo-Yervoy combination achieved a complete response rate of 21%. In the same Bristol-Myers trial, the Opdivo monotherapy achieved a complete response rate of 18%.

Nektar thinks its data mark a new high for complete responses in melanoma and sees scope for the figure to rise further still. Four patients remain on treatment and have responses that could deepen. The trial is yet to reach the median duration of response or progression-free survival. Sixteen of the 20 responses are ongoing. 

Bristol-Myers and Nektar began a phase 3 trial of the combination in untreated melanoma last year. If the phase 3 comes close to the complete response rate seen in the smaller study, the data could establish NKTR-214, also known as bempeg, in the treatment of melanoma. 

That remains a big if, though. The current data on NKTR-214-Opdivo in melanoma come from a single-arm trial of 38 patients. In contrast, the Bristol-Myers trial that linked the Opdivo-Yervoy combination to a 21% complete response rate enrolled 945 patients. Bristol-Myers and Nektar plan to enroll 764 subjects in their NKTR-214-Opdivo melanoma phase 3.

The complete response rate may go down as the size of the patient population goes up. That concern is particularly acute given memories of Incyte’s epacadostat, which achieved a 65% overall response rate when given with Opdivo in phase 2 only to come unstuck in a larger trial.

Epacadostat is a different sort of drug, though, and there are more upbeat examples of moves into late-phase trials. The Opdivo-Yervoy combination, for example, achieved a 22% complete response rate when given to 72 patients in an early melanoma trial. In phase 3, that figure ultimately came in just one percentage point lower, although the gap was bigger in early readouts.