Bristol Myers Squibb and Nektar Therapeutics said their joint Phase III PIVOT IO-001 study did not meet two endpoints: progression-free survival and objective response rate.
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Bristol Myers Squibb and Nektar Therapeutics released disappointing news about their joint Phase III PIVOT IO-001 study. The trial, which was evaluating a dual therapy of immunotherapy drug bempegaldesleukin in combination with Opdivo (nivolumab) compared with Opdivo alone to treat unresectable or metastatic melanoma, did not reach its primary endpoints.
The news is particularly harsh because Opdivo is currently involved in several other clinical trials to treat other types of cancer. This includes another trial done in conjunction with Nektar for adjuvant melanoma that BMS discontinued because of this clinical data.
The PIVOT IO-001 study has been a huge undertaking, which was both sponsored and conducted by BMS. The study involves 783 patients who received either Opdivo alone or an Opdivo/bempegaldeskleukin combination intravenously every three weeks. The results were assessed by an independent data monitoring committee.
The companies said the study did not meet two of the endpoints: progression-free survival and objective response rate. Additionally, there was no statistically significant benefit to support a third primary endpoint of overall survival. The data also failed to show any benefit to the dual therapy as opposed to Opdivo alone.
“We are disappointed with the results of this trial, which we had hoped would lead to a new therapeutic option to treat metastatic melanoma. We express our gratitude to the patients, caregivers and investigators who chose to participate in these trials,” said Jonathan Cheng, senior vice president and head of oncology development at BMS.
Because of the data, the two companies announced that they would unblind the clinical trial. No additional analyses would be performed on the overall survival endpoint. For the sake of transparency and continuous improvement, the companies said that they plan to share the data with the scientific community.
The results of the study were so clear that BMS and Nektar also decided to discontinue PIVOT-12, a Phase III open-label study evaluating the same combination of drugs on patients who have experienced complete resection of melanoma and are at a high risk of melanoma recurrence. The study, sponsored and conducted by Nektar, will be shut down immediately.
Patients in both trials are facing difficult choices due to the disappointing data. BMS and Nektar told patients they would be counseled on remaining treatment options. If the patients so choose, they can continue treatment with a physician’s approval.
However, the news isn’t just disappointing for those involved in these clinical trial—it could also be ominous for the four other studies that are currently testing Opdivo. As a checkpoint inhibitor, Opdivo is still being tested in ongoing studies on renal cell carcinoma and various bladder cancers, including urothelial cancer.
Previously, Opdivo has shown promise in several other studies. Just last week, Opdivo received approval from the U.S. Food and Drug Administration as a neoadjacant treatment for resectable non-small cell lung cancer. Last month, Opdivo received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) as a first-line treatment for esophageal squamous cell carcinoma.
However, after today’s news, the future of those other four studies could be disappointing as well. For now, all there is to do is wait.
“We will continue to await initial results from our first two ongoing studies in renal cell carcinoma and urothelial cancer, which are currently expected in the first half of 2022. We look forward to collaborating with BMS to evaluate the data from these other studies to guide the future development of bempegaldesleukin,” said Jonathan Zalevsky, chief research and development officer of Nektar Therapeutics.
If this news alone wasn’t tough enough, it also comes on the heels of a competitor’s positive news on a similar melanoma study. Merck announced last week that Keytruda, also an immunotherapy cancer drug, demonstrated significant improvement for patients in a Phase III trial for resected melanoma.
