FDA Lifts Partial Hold on CANOVA Trial for Venetoclax in Myeloma

The phase III CANOVA clinical trial — which is examining venetoclax (Venclexta) plus dexamethasone in patients with relapsed/refractory myeloma – can now continue, as the FDA lifted its partial clinical hold on the study earlier this week.

The hold, which was announced in March 2019, was for all trials examining venetoclax for the investigational treatment of myeloma. It was based on findings from the phase III BELLINI trial, investigating venetoclax with bortezomib (Velcade) and dexamethasone compared to placebo plus venetoclax and dexamethasone.

The study data showed that there were a higher proportion of deaths in the venetoclax arm compared to the control arm, 21% and 11%, respectively. The majority of patients (45%) died of progressive disease, and the percentage of serious adverse events and infection were comparable between the 2 arms.

But now, investigators on the CANOVA trial are free to start recruiting again, after study protocol was lifted, with new risk mitigation measures, protocol-specific guidelines, and updated futility criteria wer added.

"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," said Mohamed Zaki, M.D., PhD, global head of hematology development, AbbVie, the co-manufacturer of venetoclax, in a statement.

CANOVA is investigating venetoclax plus dexamethasone to pomalidomide (Pomalyst) for the treatment of patients with relapsed or refractory myeloma who have a translocation(11;14) — referred to as t(11:14) – abnormality.

To be eligible, patients must:

• Have measurable disease at screening
• Have had 2 or more prior lines of therapy
• Have had 2 or more cycles of a proteasome inhibitor and be refractory
• Be positive for t(11;14)
• Have an ECOG performance status of 2 or less

The primary endpoint of CANOVA is progression-free survival (PFS), 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 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.