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.
Key Takeaways From QOL and Use of Steroids With IO-Based RCC Regimens
May 6th 2024During a Case-Based Roundtable® event, Ulka Vaishampayan, MBBS, discussed the safety and quality-of-life data for ipilimumab plus nivolumab in patients with advanced renal cell carcinoma in the second article of a 2-part series.
Read More
Enhancing Precision in Immunotherapy: CD8 PET-Avidity in RCC
March 1st 2024In this episode of Emerging Experts, Peter Zang, MD, highlights research on baseline CD8 lymph node avidity with 89-Zr-crefmirlimab for the treatment of patients with metastatic renal cell carcinoma and response to immunotherapy.
Listen
Comparing Choices for IO/TKI Combinations in Advanced RCC
May 2nd 2024During a Case-Based Roundtable® event, Shilpa Gupta, MD, led a discussion on the combination of immunotherapy and tyrosine kinase inhibitors for patients with advanced renal cell carcinoma in the second article of a 2-part series.
Read More
Beyond the First-Line: Economides on Advancing Therapies in RCC
February 1st 2024In our 4th episode of Emerging Experts, Minas P. Economides, MD, unveils the challenges and opportunities for renal cell carcinoma treatment, focusing on the lack of therapies available in the second-line setting.
Listen
Sustained Treatment-Free Survival in RCC Seen With Nivolumab and Ipilimumab
April 30th 2024Nivolumab monotherapy plus salvage nivolumab/ipilimumab demonstrated superior treatment-free survival rates among patients with advanced renal cell carcinoma, especially in patients with favorable risk profiles.
Read More
Roundtable Roundup April: Renal Cell Carcinoma
April 27th 2024In separate, live virtual events, Arnab Basu, MD, MPH, and Robert J. Motzer, MD, asked participants which therapy they would choose for a patient with clear cell renal cell carcinoma (RCC) and why they would make that choice.
Read More