Phase III CLL14 study of Venclexta and Gazyva meets endpoint in chronic lymphocytic leukemia.

Genentech/Roche announced results from the pivotal Phase III CLL14 study in previously untreated chronic lymphocytic leukemia (CLL) showing that Venclexta (venetoclax) plus Gazyva (obinutuzumab) met its primary endpoint of investigator-assessed progression-free survival (PFS). The 12-month, fixed-duration, chemotherapy-free combination reduced the risk of disease worsening or death by 65 percent compared to Gazyva plus chlorambucil (PFS, as assessed by investigator; HR=0.35; 95 percent CI 0.23-0.53; p<0.001), when given to people with previously untreated CLL who have co-existing medical conditions.

At two years, one year after stopping treatment, nearly nine out of ten patients (88.2 percent) in the Venclexta plus Gazyva arm remained progression-free, compared to 64.1 percent in the Gazyva plus chlorambucil arm. Safety for Venclexta plus Gazyva appeared consistent with the known safety profiles of the individual medicines. Common Grade 3-4 adverse events with Venclexta plus Gazyva compared to Gazyva plus chlorambucil, respectively, were low white blood cell count (52.8 percent vs. 48.1 percent) and infections (17.5 percent vs. 15.0 percent). The treatment benefit demonstrated with the Venclexta plus Gazyva combination compared to Gazyva plus chlorambucil was consistent across secondary endpoints, including an overall response of 84.7 percent vs. 71.3 percent; p<0.001), a complete response with at least partial blood count recovery (49.5 percent vs. 23.1 percent; p<0.001), minimal residual disease (MRD)-negativity in the bone marrow (56.9 percent vs. 17.1 percent; p<0.001) and peripheral blood (75.5 percent vs. 35.2 percent; p<0.001) three months after treatment.

MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells. The results were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).

See: "Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions" Kirsten Fischer et al. NEJM June 4, 2019, DOI: 10.1056/NEJMoa1815281