Carfilzomib approved in combination with dexamethasone, or with lenalidomide plus dexamethasone, for patients with relapsed/refractory multiple myeloma.
The FDA today granted approval to carfilzomib (Kyprolis) for use in combination with dexamethasone, or with lenalidomide plus dexamethasone, for patients with relapsed/refractory multiple myeloma after previous treatment with 1 to 3 lines of therapy.
The approval converts the FDA’s single-agent accelerated approval for Kyprolis in 2012 to a full approval. The prior approval of Kyprolis monotherapy was for patients with multiple myeloma who received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and who demonstrated disease progression on or within 60 days of completing the last therapy.
In July 2015, the FDA approved Kyprolis in combination with lenalidomide and dexamethasone for patients with relapsed multiple myeloma who received 1 to 3 prior lines of therapy.
"Kyprolis is the only approved therapy for relapsed multiple myeloma with proven efficacy as a single agent, doublet and triplet combination that is offered in a variety of doses to meet individual patient needs," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen, in a press release. "Importantly, this new approval supports the use of Kyprolis as a backbone therapy for the management of relapsed multiple myeloma, a difficult-to-treat blood cancer."
Today’s approval followed results of the phase 3 ENDEAVOR study, which showed Kyprolis and dexamethasone decreased progression risk by 47% compared with bortezomib (Veclade) and dexamethasone. Median progression-free survival (PFS) with Kyprolis was 18.7 months, compared with 9.4 months on bortezomib (HR, 0.53; 95% CI, 0.44-0.65; P <.0001).
The study randomized 929 patients with a median age of 65 years to receive Kyprolis as a 30-minute infusion along with dexamethasone (n = 464) or Veclade and dexamethasone (n = 465). Kyprolis was administered at a starting dose of 20-mg/m2 on days 1 and 2 of the first cycle. If tolerated, the dose was increased to 56-mg/m2 on day 8 of the first cycle.
The 56-mg/m2 dose was subsequently maintained on days 9, 15, and 16 and throughout subsequent cycles. Patients in the control arm received Veclade at 1.3-mg/m2, with 75% administered Veclade subcutaneously.
The primary endpoint was PFS, with overall survival (OS), objective response rate (ORR), duration of response, and safety as secondary measures.
The PFS advantage from Kyprolis was consistent across treatment subgroups. Median OS was 24.3 months in the Kyprolis cohort, but was not yet reached in the Kyprolis cohort (HR, 0.79; P = .066). At the time of primary analysis, survival data was not yet mature.
ORR was 77% in the Kyprolis group compared with 29% in the Veclade group. The complete response rate in the Kyprolis arm was 13% compared with 6% in the Veclade arm. The rate of very good partial response or better in the Kyprolis cohort was 54% versus 29% in the Veclade cohort.
Grade 3 adverse events were reported more frequently in the Kyprolis cohort compared with Veclade (73% vs 67%). Serious adverse events were also more common with Kyprolis (48% vs 36%). Meanwhile, dose reductions associated with adverse events were more common with Veclade compared with Kyprolis (48% vs 23%). Treatment discontinuation from adverse events and on-study deaths were comparable among both treatment groups.