Results presented from phase III CANOVA study of venetoclax in patients with r/r multiple myeloma

Data did not demonstrate that the treatment combination significantly improved progression-free survival (PFS), the primary endpoint of the trial.

Patients receiving VenDex showed improvement in median PFS of 9.9 months compared to 5.8 months with the combination of study comparator pomalidomide and dexamethasone (PomDex); however, the results did not reach statistical significance [HR = 0.823, 95% CI: (0.596, 1.136); p-value of 0.237].

Select prespecified secondary endpoints from the CANOVA trial include the following: i. Overall response rate (ORR): 62% in VenDex vs. 35% in PomDex (nominal p-value of <0.001). ii. rate of very good partial response or better (vgpr) at 39% in vendex vs. 14% in pomdex (nominal p-value of><0.001). iii. median overall survival (os) was 32.4 months in vendex vs. 24.5 months in pomdex [hr of 0.697 (95% ci: 0.472, 1.029); nominal p-value of 0.067].

Additional prespecified analyses include: i. PFS per investigator which resulted in a median PFS of 9.1 months with VenDex vs 4.9 months with PomDex [HR = 0.737, (95% CI: 0.543, 1.000); nominal p-value of 0.050] ii. Median time to next treatment (TTNT) which was longer in the VenDex arm 21.2 months vs. 8.3 months in the PomDex arm [HR of 0.546 (95% CI: 0.385, 0.776); nominal p-value of 0.001].

The safety profile of the combination of venetoclax and dexamethasone in the trial was generally consistent with the known safety profiles when used as single agents and no new safety signals have emerged. The most common adverse events (AEs) experienced by patients (greater than 20%) treated with VenDex included any infection (61%), diarrhea (41%), lymphopenia (24%) and nausea (22%). The most common AEs experienced by subjects treated with PomDex included neutropenia (63%), any infection (57%), thrombocytopenia (39%) and anemia (35%).

Multiple myeloma is the second most common blood cancer in the world. Many patients experience poor outcomes as most eventually relapse despite recent treatment advances. A subset of patients have the t(11;14) biomarker, the most common chromosomal translocation in multiple myeloma, that can signal an overexpression of the BCL-2 protein.

"While the CANOVA trial did not meet its primary endpoint, given the potential favorable trends seen in the study, we will discuss these data with health authorities in the near future," said Mariana Cota Stirner, M.D., Ph.D., therapeutic area head oncology hematology, AbbVie. "We remain committed to elevating the standard of care for blood cancer patients around the world including patients with multiple myeloma."