PIVOT-09 trial examining bempegaldesleukin plus nivolumab in patients with renal cell carcinoma and bladder cancer has been discontinued.
The clinical development program, PIVOT-09 (NCT03729245), examining bempegaldesleukin (BEMPEG; NKTR-214) in combination with nivolumab (Opdivo) in renal cell carcinoma (RCC) and bladder cancer has been discontinued, according to Nektar Therapeutics and Bristol Myers Squibb.1
All other studies of the combination, including a study in muscle-invasive bladder cancer (CA045-009, NCT04209114), a phase 1/2 study of the doublet in combination with tyrosine kinase inhibitor (TKI) therapy in 1L RCC (CA045-011, NCT04540705), and a phase 1/2 study in recurrent and/or refractory pediatric tumors (CA045-020, NCT04730349), will be discontinued as well.
“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,” said Jonathan Cheng, senior vice president and head of oncology development at Bristol Myers Squibb, in the press release. “We are immensely grateful to the patients and investigators who participated in these studies.”
The phase 3 PIVOT-09 study aimed to evaluate patients with previously untreated advanced or metastatic RCC by comparing the objective response rate (ORR) and overall survival (OS) of BEMPEG combined with the PD-1 immune checkpoint inhibitor, nivolumab, to that of TKI monotherapy in this patient population.2
The randomized trial enrolled 623 patients with previously untreated RCC who had a Karnofsky performance status of at least 70%, measurable disease per mRECIST 1.1 criteria, no prior systemic therapy for RCC, and histologically confirmed RCC with a clear-cell component. Additionally, patients had advanced or metastatic RCC which was not amenable to curative surgery or radiation therapy and those with any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score were eligible given that at least one IMDC prognostic factor was present.
Those in the experimental arm received a combination of BEMPEG at 0.006 mg/kg plus nivolumab intravenously at 360 mg every 3 weeks while patients in arm B received the investigator's choice of either sunitinib or cabozantinib. Treatment was continued until disease recurrence, unacceptable toxicity, or withdrawal of consent for up to 24 months.
Primary end points of the trial were ORR and OS with secondary end points including progression-free survival, incidence of adverse events, health outcomes, quality of life, and PD-L1 expression on tumor cells.
According to an Independent Data Monitoring Committee the final analysis of ORR as assessed by Blinded Independent Central Review (BICR) showed that the combination of BEMPEG plus nivolumab did not meet the prespecified boundary for statistical significance in comparison to the control arm. Additionally, the interim analysis of OS in either population also did not meet the prespecified boundary for statistical significance. Due to no clinical benefit shown in the doublet therapy arm vs the TKI arm, the trial has been ended with no further analyses for the OS end point.
Further, the separate phase 2 trial, PIVOT-10 (NCT03785925), investigated BEMPEG plus nivolumab in patients with cisplatin-ineligible, locally advanced or metastatic urothelial cancer, including those whose baseline tumor cells express low levels of PD-L1. Findings showed that the combination did not reach an efficacy threshold in its final ORR analysis, leaving no support for 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.