New Drug Combinations Show Promising Results, an Orphan Drug Designation, and the FDA Speeds International Approvals
The phase III CANDOR clinical trial has met its primary endpoint, according to a Sept. 13 announcement by Amgen. The endpoint was improved progression-free survival (PFS), which was 15.8 months for the doublet of Kyprolis+dexamethasone versus the triplet of Kyprolis+Darzalex+dexamethasone (D-Kd), for which the PFS was not yet reached. This represented a 37% reduction in risk of relapse or death in this population of patients with relapsed/refractory myeloma.
This very important trial involved 466 patients and demonstrated benefit with a unique proteasome inhibitor/monoclonal antibody combination. The inclusion of Kyprolis is especially beneficial in patients with higher-risk disease (versus, for example, the MAIA trial combination of Darzalex+Revlimid+dexamethasone, which produced excellent results but less striking benefit for higher-risk patients). The phase III CANDOR trial results support the earlier single-arm study results with the D-Kd triplet, using a once-per-week schedule for the Kyprolis instead of a twice-weekly schedule. This once-per-week schedule can certainly make the combination more attractive for both patients and physicians.
Trial results will be presented in full at a later date and will be the basis of an upcoming FDA submission. It is great to see an important new combination move forward in a positive fashion.
GRIFFIN study results reported
Among the many presentations at the recently concluded 17th International Myeloma Workshop in Boston were the results from the GRIFFIN study, which demonstrated the added benefit of combining Darzalex with Velcade+Revlimid+dexamethasone (D-VRd) in the frontline setting. In this randomized phase II trial, patients were assessed after six cycles of induction therapy followed by autologous stem-cell transplant (ASCT). In this comparison of D-VRd versus VRd, 42% of patients achieved stringent complete response (sCR) versus 32% with VRd alone. Truly deep responses were also greater, with 59% of patients in CR or better becoming MRD negative, versus only 24% with the VRd alone. Definitely encouraging data with this four-agent combination!
‘Orphan’ designation for myeloma drug
Orphan Drug status was announced for GBR 1342 this week. GBR 1342 is a novel agent called a BEAT rather than a BiTE. This BEAT is a bispecific engagement antibody T cell receptor agent. Like a BiTE (a bispecific T cell engager), this agent cross-links CD 38 on the myeloma cells with CD 3 on the surface of T cells to enhance the T cells’ anti-myeloma efficacy. The studies are just starting to find the best dose and scheduling, evaluate efficacy, and determine potential toxicities. Initial dosing is a 24-hour infusion, twice-weekly, versus, for example, the Amgen 420 BiTE, which has used a 24-hour infusion for 28 days. This new “BEAT” is interesting and potentially promising for patients desperately needing new options now and, more broadly, in the future.
Swifter international approvals for cancer drugs
In an announcement this week with global implications, the U.S. Food and Drug Administration (FDA) revealed a new program called Project Orbis, designed to accelerate drug approvals for cancer agents. The project allows new drug results to be submitted simultaneously to the U.S., Canadian, and Australian agencies for review and potential approval . As noted by Dr Richard Pazdur, director of FDA’s Oncology Center of Excellence, “It’s important to me that good medications are available not just to citizens of the U.S. but all over the world.” We will be following this development closely to see if real benefits in patient access emerge.
Dr. Brian G.M. Durie co-founded and now serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.