The Food and Drug Administration lifted a partial clinical hold on the CANOVA trial, examining Venclexta plus dexamethasone for some patients with relapsed/refractory myeloma.
The Food and Drug Administration (FDA) lifted a partial clinical hold on the phase 3 CANOVA trial examining Venclexta (venetoclax) plus dexamethasone for the treatment of patients with multiple myeloma.
The CANOVA trial is comparing Venclexta plus dexamethasone to Pomalyst (pomalidomide) for the treatment of patients with relapsed or refractory myeloma who have a translocation(11;14) — referred to as t(11;14) – abnormality. The clinical hold was lifted after study protocol was revised, with new risk mitigation measures, protocol-specific guidelines, and updated futility criteria. Now, institutions involved in CANOVA can resume enrollment.
To be eligible to enroll, patients must have measurable disease at screening; have two or more prior lines of therapy; had two or more consecutive cycles of Revlimid (lenalidomide) and be refractory to the drug; have two or more cycles of a proteasome inhibitor; be positive for t(11;14); and have an ECOG performance status of 2 or less.
The primary endpoint of CANOVA is progression-free survival, and secondary endpoints are very good partial response or better response rate, overall response rate, overall survival, duration of response, time to disease progression, time to response and quality of life.
"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," Dr. Mohamed Zaki, global head of hematology development at AbbVie, the co-manufacturer of Venclexta, said in a statement.
AbbVie originally announced the FDA’s partial clinical hold in March 2019. The hold was for all trials evaluating Venclexta for the investigational treatment of myeloma, and occurred after a data review of the phase 3 BELLINI trial, which investigated Venxlexta with Velcade (bortezomib) and dexamethasone compared to placebo plus Velcade and dexamethasone in patients with relapsed or refractory myeloma who had one to three prior lines of therapy.
BELLINI data showed that there were a higher proportion of deaths in the Venclexta arm (21%) than the control arm (11%). The most common cause of death was progressive disease, occurring in 45% of patients. The percent of serious side effects and serious infections were comparable between the two arms.
Venclexta is approved for other hematologic malignancies, including chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), but does not yet have any indications in the myeloma space.
"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,” Zaki said.