The FDA has removed the partial clinical hold it placed on AbbVie’s CANOVA (M13-494) study, according to a statement from the company. CANOVA was designed to investigate venetoclax (Venclexta or Venclyxto) for the treatment of relapsed and refractory multiple myeloma (MM) patients with a specific genetic mutation.
Regulators lifted the partial clinical hold based upon an agreement that the study protocol would be revised. Changes included new risk mitigation measures, protocol-specified guidelines, and updated futility criteria. Researchers may now continue enrollment for the study based on the approved protocol.
CANOVA, a multicenter, randomized, open-label, phase 3 trial, was being conducted to examine the efficacy of venetoclax combined with dexamethasone, compared to pomalidomide combined with dexamethasone, in patients with relapsed and refractory MM who were positive for the translocation (11;14) abnormality. The t(11;14) biomarker is 1 of the most prevalent, regularly tested genetic abnormalities among patients with MM.
The FDA ordered the partial clinical hold on all venetoclax-related trials in March 2019 when results from the BELLINI study showed a disproportionate number of deaths had occurred among participants treated with venetoclax compared to the number of deaths that occurred among participants who received placebo.
BELLINI was a phase 3, randomized, double-blind, controlled trial of bortezomib and low-dose dexamethasone with or without venetoclax in patients with relapsed and refractory MM who previously received 1 to 3 lines of therapy. At the interim analysis for overall survival in BELLINI, there were 41 deaths reported among 194 patients in the venetoclax-treated study arm while 11 deaths were reported among 97 patients in the placebo-treated arm. Progressive disease was the most common cause of death in 45% of participants.