ASCO18: Bristol-Myers Squibb, Nektar advance Opdivo, NKTR-214 combination into late-stage testing

Bristol-Myers Squibb and Nektar Therapeutics announced plans to move the experimental drug NKTR-214 into late-stage development for a number of tumour types, including melanoma and renal cell carcinoma, based on preliminary results from a Phase I/II study. Mary Tagliaferri, chief medical officer at Nektar, said "we've observed important responses, including activity in PD-L1 negative patients," in the PIVOT trial, which is investigating NKTR-214 in combination with Bristol-Myers Squibb's Opdivo (nivolumab).

At the American Society of Clinical Oncology (ASCO) annual meeting, the companies reported safety, efficacy and biomarker data for patients enrolled in the Phase 1 dose-escalation stage of the PIVOT study and for the first patients enrolled in select dose expansion cohorts in Phase 2 as of May 29. The companies noted that the trial is designed with efficacy targets separately pre-defined for each tumour type, which if met in either stage of the study means that the combination regimen would be advanced to registrational studies in that tumour type.

Results in treatment-naïve patients with Stage IV metastatic melanoma showed that the objective response rate (ORR) in the first part of the study was 85 percent in 13 treated subjects, while responses were observed in 50 percent of 28 patients in stage two of the trial, including three complete responses and 10 partial responses. Bristol-Myers Squibb and Nektar added that among 25 patients with known PD-L1 status, the ORR in PD-L1 negative tumours was 42 percent and in PD-L1 positive patients it was 62 percent. 

Commenting on results for the second stage of the trial in melanoma, which saw only three additional responses compared to the first part of the study, Nektar chief scientific officer Jonathan Zalevsky suggested that the new patients had simply not been on the drug long enough to respond.

Further, data showed that in treatment-naïve patients with Stage IV metastatic renal cell carcinoma, the ORR in stage one of the study was 64 percent in 11 treated subjects, while responses were seen in 46 percent of 26 patients in the second phase of the trial. The drugmakers noted that in the 24 patients with known PD-L1 status, the ORR in PD-L1 negative tumour was 53 percent and 29 percent in PD-L1 positive subjects.

Finally, results in treatment-naïve patients with Stage IV metastatic urothelial carcinoma showed that the ORR in the first part of the study was 60 percent in 10 treated subjects, with the same response rate in both PD-L1 negative patients and in those with PD-L1 positive tumours. Bristol-Myers Squibb and Nektar indicated that they plan to initiate a Phase III study of NKTR-214 in combination with Opdivo in first-line advanced melanoma patients in the third quarter, while pivotal trials are also being designed in renal cell carcinoma and urothelial cancer. 

The companies added that overall in the study, at week three, 53 percent of 17 patients with a PD-L1 negative status at baseline were converted to PD-L1 positive status. Results showed that of these subjects, 78 percent achieved either stable disease, partial response or a complete response.

Commenting on the data, Fouad Namouni, head of oncology development at Bristol-Myers Squibb, said they "support our belief that NKTR-214…in combination with Opdivo can potentially expand the treatment benefits we can bring to patients with cancer." The companies added that enrolment is also continuing in the second stage of the PIVOT trial with over 400 patients with melanoma, renal cell, urothelial, non-small-cell lung and triple negative breast cancers.

Earlier this year, Bristol-Myers Squibb paid $1 billion upfront as part of a deal potentially worth over $3.6 billion to develop Nektar's NKTR-214. The CD122-biased agonist is designed to selectively expand T cells and natural killer cells directly in the tumour micro-environment and increase PD-1 expression on those immune cells.

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