What have Kyprolis clinical trials shown?
Kyprolis® (carfilzomib, Onyx) clinical trials have revealed positive effects on treating myeloma as well as manageable side effects.
Kyprolis was initially granted FDA approval for treatment of patients with relapsed or refractory multiple myeloma based on the results of a large Phase II study (PX-171-003-A1) involving 266 patients who had received an average of five myeloma therapies prior to entering this trial.
- 24% of patients achieved a partial response or better with Kyprolis
- On average responses lasted 7.8 months
- Average survival was 15.6 months
In another Phase II trial (PX-171-004) involving 165 patients with relapsed or refractory multiple myeloma after 1 to 3 therapies, Kyprolis provided one of the highest single-agent response rates and longest response duration reported in this patient population. Results were assessed both for those who had never and who had previously received Velcade® (bortezomib, Takeda Oncology).
Of the 129 patients who had never received Velcade, the overall response was 42%. 14% had a very good partial response and 25% had a partial response
- The overall response increased to 52% with a higher dose of Kyprolis
- Responses were durable, lasting a median of 13.1 months
- In the patients who had previously received Velcade but stopped responding to it, the overall response was 17%
- Average duration of response was 11.5 months
- Median time until the disease started to progress was 8.1 months
The Multiple Myeloma Research Consortium (MMRC), an affiliate organization of the MMRF that accelerates early-stage clinical trials, played a pivotal role in these clinical studies. For PX-171-003-A1, the MMRC enrolled nearly 60% of patients, yet represented just one-third of the total sites. Similarly, in study PX-171-004, MMRC member institutions enrolled approximately 44% of patients who participated.
Kyprolis in combination with Revlimid and dexamethasone
The combination of Kyprolis, Revlimid® (lenalidomide, Celgene), and low-dose dexamethasone (KRd) was approved for use in patients with relapsed myeloma based on the results of the ASPIRE trial. This international Phase 3 trial included 792 patients who had received one to three prior treatment regimens.
- Patients receiving KRd lived 50% longer (8.7 months longer) without their disease worsening compared to patients receiving Revlimid-low-dose dex (Rd) alone.
- Progression-free survival was 26.3 months in the KRd group compared to 17.6 months in the Rd group.
- The overall response rate was 87% in the KRd group and 67% in the Rd group.
- A higher percentage of patients in the KRd group achieved a stringent complete response (sCR) than in the Rd group (14% vs. 4%).
Kyprolis in combination with dexamethasone
An international Phase 3 trial known as ENDEAVOR was one of two head-to-head Phase 3 trials comparing Kyprolis and Velcade. The study included 929 patients whose myeloma had relapsed after at least one, but not more than three, prior treatment regimens. Patients received either Kyprolis or Velcade in combination with low-dose dexamethasone.
Results from the study show that:
- Patients receiving Kyprolis-low-dose dex lived twice as long without their disease progressing.
- Progression-free survival was 18.7 months compared with 9.4 months with Velcade-dex (P<0.0001)
- Patients in the Kyprolis-low-dose dex group also had a significantly higher overall response rate than the Velcade-low-dose dex group (77% vs. 63%, P<0.0001).
- Patients receiving Kyprolis-low-dose dex demonstrated improved progression-free survival and overall response rate over those receiving Velcade-low-dose dex regardless of number of previous treatments or previous exposure to either Revlimid or Velcade. [Moreau ASH 2015 Abstract 729]
- Results from this study led to the approval of Kyprolis and low-dose dexamethasone for use in patients with relapsed or refractory myeloma who had received at least 1 to 3 previous treatments.
How is Kyprolis currently being studied in myeloma?
Kyprolis is being evaluated in combination with other agents in a number of ongoing clinical trials in relapsed and/or refractory myeloma, as well as in newly diagnosed disease and smoldering multiple myeloma, and as maintenance therapy.
Several Phase 3 trials are being conducted, including studies evaluating:
- KRd compared with Velcade-Rd in patients with newly diagnosed myeloma
- Kyprolis, melphalan, and prednisone compared with Velcade, melphalan, and prednisone in patients with newly diagnosed myeloma. This international study known as CLARION is the second head-to-head Phase 2 trial comparing Kyprolis and Velcade and has completed enrollment.
- Kyprolis and dexamethasone given on a once-weekly or a twice-weekly dosing schedule in patients with relapsed and refractory myeloma (ARROW study)
- KRd compared with Revlimid as maintenance therapy after autologous stem cell transplantation [NCT02659293]
Interested in learning more about Kyprolis clinical trials? Talk to an MMRF Patient Support Nurse to learn more or use our clinical trials finder: