FDA Lifts Hold on CANOVA Venetoclax Trial in Myeloma
The FDA has now lifted the partial hold on the Phase III CANOVA multiple myeloma trial using venetoclax with pomalidomide and dexamethasone. Venetoclax is a BCL-2 inhibitor that is being jointly developed between AbbVie and Roche. The hold was lifted after additional risk mitigation procedures and the implementation of new guidelines.
Certain myeloma venetoclax studies went on a recruiting hold based on data from the BELLINI trial that combined venetoclax with bortezomib and dex, when more patient deaths were seen on the study arm with venetoclax. The BELLINI trial is a joint venture between AbbVie and Genentech.
The venetoclax trials are of great interest in multiple myeloma because it is the first drug that appears to have specific impact for translocation 11;14 myeloma patients. In the press release, Mohamed Zaki, MD, PhD, global head of hematology development at AbbVie said:
"We are pleased to move forward with the CANOVA study which, with the t(11;14) biomarker test, can help identify patients who may respond better to treatment and add clarity for physicians when choosing a therapy, if approved. We are working closely with regulatory authorities worldwide to continue our efforts to understand the potential of venetoclax for patients with multiple myeloma while continuing to advance research in patients with the t(11;14) genetic abnormality."
The re-opening of the CANOVA trial does not apply to other myeloma clinical trials using venetoclax. It also does not affect the venetoclax FDA-approvals already in place for CLL and AML leukemia patients.
The most updated results of the Phase III BELLINI trial were presented at the 2019 European Hematology Association Congress and included the following:
- Progression free survival (the time on treatment without disease progression) as 22.4 months on the venetoclax/bortezomib/dex arm vs. 11.5 months on the bortezomib/dex arm.
- The median response was not yet reached in the venetoclax arm vs. 12.8 months in the bortezomib/dex arm.
- Shorter progression free survival was seen for patients with high risk myeloma genetics or low BCL-2 expression
- There were 40 deaths in the venetoclax combination group
- There were 11 deaths in the bortezomib/dexamethasone–only group
- The majority of deaths in both arms were caused by progressive disease and occurred after 30 days of the last dose
Authors of the BELLINI study suggest that venetoclax can provide clear benefit for 11;14 patients, but that only 11;14 myeloma patients be included in future venetoclax studies until more data emerges.