Following data earlier this year that saw flagging overall response rates in late-stage melanoma, Nektar Therapeutics unveiled new, highly anticipated clinical results for its combination of NKTR-214 and Opdivo that showed rates holding just about steady in a larger number of patients.
At the annual meeting of the Society for Immunotherapy of Cancer, the company’s phase 1/2 PIVOT trial delivered a confirmed best overall response rate of 53%, or 20 of 38 evaluable first-line patients with stage 4 melanoma, including nine complete responses.
That tracks with data presented at the ASCO annual meeting this summer, which demonstrated an ORR of 50%, or 14 of 28 patients.
Prior to the meeting in Chicago, an abstract had shown drops in overall response rates for three cancers compared to a study readout from November 2017—including a fall from 85%, or 11 of 13 patients, in melanoma. At the time, the company said that patients in the early dataset hadn’t received the therapy long enough to register proper responses.
The new SITC data, with a cutoff of Oct. 1, had a median time to response of 2 months, with 17 of the 20 patients demonstrating ongoing responses after a median follow-up of 7.2 months. The ORR in patients testing negative for PD-L1 was 43%, but reached 68% in positive patients.
Additionally, the disease control rate was 76%, Nektar said, with Chief Scientific Officer Jonathan Zalevsky describing the results as evidence of “deep and durable responses” in melanoma patients that had not received a previous immunotherapy.
Meanwhile, eight of the study’s 41 treated patients experienced a Grade 3 or higher adverse event, with two discontinuing therapy due to increases in blood creatine and a stroke. Another two had a grade 3 or higher immune-mediated event, but neither stopped their treatment. Low-grade cytokine related events decreased frequency under continuous dosing.
In the company’s SITC oral presentation, results showed that NKTR-214 helped traffic new T cell clones into the tumor microenvironment, with patients demonstrating new clones after three weeks that were not present at baseline. In addition, the combination also promoted favorable changes in anti-tumor gene expression, including in CTLA4 and PD-1 T-cell activation receptors, as well as reductions in melanoma tumor antigen over the same three-week period.
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NKTR-214, a CD-122 agonist designed to stimulate the patient’s immune system via the IL-2 pathway, to increase the number of tumor-infiltrating white blood cells. Along with Bristol-Myers Squibb's PD-1 inhibitor Opdivo, the PIVOT study is also studying the combination’s effects in renal cell carcinoma, urothelial carcinoma, non-small cell lung cancer and triple-negative breast cancer.
And with NKTR-214 serving as the main foundation of Nektar’s pipeline, clinical successes are essential for the multibillion-dollar company. A phase 3 trial of NKTR-214 and Opdivo in first-line melanoma, which aims to enroll over 760 patients, is already underway.
Nektar and BMS first teamed up on combination trials in 2016, after Opdivo failed a phase 3 trial in NSCLC.
In February, BMS committed $3.6 billion to develop NKTR-214 in combination with Opdivo and Yervoy, with $1 billion upfront, a purchase of $850 million in Nektar stock and the promise of up to $1.8 billion in potential milestones.