AbbVie’s ibrutinib, venetoclax combo succeeds in phase 3 GLOW study
AbbVie said that the phase 3 GLOW study in chronic lymphocytic leukemia (CLL) investigating the combination of IMBRUVICA (ibrutinib) plus VENCLEXTA/VENCLYXTO (venetoclax) (I+V) has met its primary endpoint of superior progression-free survival (PFS).
The GLOW clinical trial is comparing the efficacy and safety of the ibrutinib, venetoclax combination against chlorambucil plus obinutuzumab (C+O) for first-line treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study is in patients who had active disease that requires treatment per the International Workshop on CLL (iwCLL) criteria.
A total of 211 patients are involved in the late stage clinical trial, who were randomly grouped in a 1:1 ratio to be administered with the ibrutinib, venetoclax combo or chlorambucil plus obinutuzumab.
The primary endpoint of PFS as assessed by an independent review committee, showed a reduction in the risk of disease progression or death for the investigational combination by nearly 78% compared to the chlorambucil, obinutuzumab combination.
According to AbbVie, the median PFS was 21 months for chlorambucil plus Obinutuzumab, while the median PFS for the ibrutinib, venetoclax combo had not been reached at the time of analysis.
The safety profile of ibrutinib, venetoclax combination was generally in line with the safety profile of the constituent agents while the tolerability profiles were consistent with treatment of CLL in the enrolled patient population.
Secondary endpoints of the phase 3 GLOW clinical trial included rates of undetectable minimal residual disease (uMRD), overall response rate (ORR), and complete response rate (CR).
The uMRD rate in the bone marrow as evaluated by next generation sequencing was considerably higher for patients on ibrutinib, venetoclax combination compared to those treated with chlorambucil plus obinutuzumab. Three months following the completion of treatment, uMRD was observed in 51.9% and 17.1%, respectively.
The CR rate was also substantially higher with the ibrutinib, venetoclax combination. However, the ORR did not show a significant difference between the two patient groups.
Mohamed Zaki – vice president and head, global oncology development, AbbVie said: “We are encouraged by these results, which further support the efficacy of these two well-established therapies.
“We remain steadfast in our commitment to continue the research and development of this combination as a potential treatment for CLL with the ultimate goal to put patients into remission with a fixed-duration, oral therapy.”
Ibrutinib is a BTK inhibitor, which has been jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech. It is approved for the treatment of chronic lymphocytic leukemia and five other disease areas.
On the other hand, venetoclax, is an approved blood cancer drug, which inhibits the B-cell lymphoma-2 (BCL-2) protein. It was developed by AbbVie and Roche.