Nektar Therapeutics and Bristol Myers Squibb announced that based on results from pre-planned analyses of two late-stage clinical studies of bempegaldesleukin (BEMPEG) in combination with Opdivo (nivolumab) in renal cell carcinoma (RCC) and bladder cancer, the companies have jointly decided to end the global clinical development program for bempegaldesleukin in combination with Opdivo.
These studies and all other ongoing studies in the program will be discontinued.
In the Phase 3 PIVOT-09 study in patients with previously untreated advanced or metastatic RCC, Nektar and Bristol Myers Squibb were informed by an independent Data Monitoring Committee (DMC) that a final analysis of objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) showed that bempegaldesleukin in combination with Opdivo did not meet the prespecified boundary for statistical significance in comparison to the tyrosine kinase inhibitor (TKI) control arm in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk or all-risk populations. An interim analysis of overall survival (OS) also did not meet the prespecified boundary for statistical significance in either of these populations. Given there was no clinical benefit in the doublet therapy arm compared to the TKI arm, the companies have decided to unblind the trial and to perform no additional analyses for the OS endpoint.
In the separate Phase 2 PIVOT-10 study of the bempegaldesleukin/Opdivo doublet in patients with cisplatin-ineligible, locally advanced or metastatic urothelial cancer, a final ORR analysis assessed by BICR showed that bempegaldesleukin in combination with Opdivo did not reach an efficacy threshold to support continuing the program in urothelial carcinoma.
The companies will review the data for both studies and plan to share the results with the scientific community.
All other studies of bempegaldesleukin in combination with Opdivo, including a pivotal study in muscle-invasive bladder cancer (CA045-009), a Phase 1/2 study of the doublet in combination with TKI therapy in 1L RCC (CA045-011) and a Phase 1/2 study in recurrent and/or refractory pediatric tumors (CA045-020), will be discontinued, allowing patients and their physicians to consider standard of care treatment options for their specific conditions.
Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers Squibb, said:
As a leader in developing innovative therapies for patients with cancer, we are committed to continuing to explore novel combinations and pathways and advancing research that may help cancer patients achieve better outcomes. We are immensely grateful to the patients and investigators who participated in these studies.
The companies previously announced in March that two pivotal studies in melanoma would be discontinued based on results in the Phase 3 PIVOT IO-001 study in metastatic melanoma. Over the coming months, the companies will work jointly to discontinue the clinical program for bempegaldesleukin in combination with Opdivo.
Jonathan Zalevsky, chief research and development officer of Nektar Therapeutics, said:
We thank BMS for their collaboration on the studies of bempegaldesleukin. Nektar remains dedicated to the development of therapeutics to treat cancer and auto-immune disease.