The breakthrough therapy designation will expedite the development and review of Opdivo in advanced renal cell carcinoma.
Opdivo (nivolumab) has received an FDA breakthrough therapy designation for the treatment of patients with advanced renal cell carcinoma (RCC), according to Bristol-Myers Squibb, the manufacturer of the immunotherapy.
The designation, which will expedite the development and review of Opdivo in RCC, is based on the CheckMate-025 trial. The phase 3 study was stopped early in July after an independent panel determined that Opdivo improved overall survival (OS) versus everolimus (Afinitor) in patients with advanced RCC. The CheckMate-025 data will be presented at the 2015 European Cancer Congress, according to Bristol-Myers Squibb, which also announced its intent to file for regulatory approval this year.
“Results from CheckMate-025 mark the third tumor in which Opdivo has shown an overall survival benefit in a phase 3 trial," Michael Giordano, senior vice president, head of development, Oncology, at Bristol-Myers Squibb, said in a statement. "The breakthrough therapy designation in advanced renal cell carcinoma is a clear signal of the need for additional treatment approaches for RCC and reflects part of our broad commitment to immuno-oncology research that may address many types of advanced cancers."
The open-label, parallel assignment CheckMate-025 trial randomized 821 previously treated patients with advanced or metastatic clear-cell RCC to 3 mg/kg of intravenous Opdivo every two weeks or 10 mg of oral Afinitor (everolimus) daily until progression or unacceptable toxicity. Prior treatment with one or two antiangiogenic treatment regimens for advanced or metastatic disease was required, along with evidence of disease progression within six months of enrollment.
OS was the primary endpoint, with secondary outcome measures including objective response rate (ORR) and progression-free survival (PFS). When the trial was halted after meeting its primary endpoint, eligible patients in the everolimus cohort were allowed to cross over and receive Opdivo in an open-label extension of the study.
Previously published phase 2 data demonstrated clinical activity for Opdivo with acceptable toxicity in 168 patients with metastatic RCC (mRCC) who had previously received anti-VEGF therapy.1 Seventy percent of patients in the study (118 patients) had received more than one prior systemic regimen.
In a blinded 1-to-1-to-1 randomization, patients received either 0.3 (60 patients), 2.0 (54 patients), or 10 mg/kg (54 patients) of intravenous Opdivo once every three weeks. PFS was the primary outcome measure, with secondary endpoints including ORR and OS.
In order of increasing dosage, median PFS was 2.7, 4.0 and 4.2 months, respectively, with ORRs of 20 percent, 22 percent and 20 percent. In the three treatment arms, median OS was 18.2 months, 25.5 months and 24.7 months, respectively.
Fatigue was the most frequently reported adverse event (AE), with rates of 24 percent, 22 percent and 35 percent, in the 0.3-, 2.0- and 10-mg/kg cohorts, respectively. Grade 3/4 treatment-related AEs were reported for 11 percent of patients (19 patients) in the overall study population.
Opdivo is the second drug to recently receive a breakthrough designation from the FDA for the treatment of patients with kidney cancer. In August, breakthrough status was granted to the multikinase inhibitor Cometriq (cabozantinib) as a treatment for patients with advanced RCC following one prior therapy.
Opdivo was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor. In March 2015, the PD-1 inhibitor was approved for the treatment of patients with advanced squamous non—small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy.
The FDA is currently reviewing applications for frontline Opdivo as a monotherapy and in combination with Yervoy for patients with advanced melanoma, as well as an indication for patients with previously treated nonsquamous NSCLC.
Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430-1437.