The Calquence, obinutuzumab combination registered a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) during the trial, which was the primary endpoint. This was in comparison to the chemotherapy-based combination of chlorambucil and obinutuzumab.
The late stage trial featured 535 patients who were randomised in a 1:1:1 ratio in three groups.
Patients in the first arm were subjected to the chlorambucil and obinutuzumab combination and the second arm was administered with 100mg Calquence daily twice until disease progression in combination with obinutuzumab. The third arm was subjected to 100mg twice daily of Calquence monotherapy until disease progression.
The ELEVATE-TN trial also met a key secondary endpoint with Calquence monotherapy registering a statistically-significant and clinically-meaningful improvement in PFS, in comparison to the chemotherapy and obinutuzumab combination.
AstraZeneca said that the safety and tolerability of the Bruton tyrosine kinase (BTK) inhibitor was in line with its established profile.
AstraZeneca oncology R&D executive vice president José Baselga said: “These findings confirm the superiority of Calquence as a monotherapy and also in combination over standard-of-care treatments for chronic lymphocytic leukaemia. The positive results from both the ELEVATE-TN and ASCEND trials will serve as the foundation for regulatory submissions later this year.”
Last month, the blood cancer drug met its primary endpoint at interim analysis in the phase 3 Ascend (ACE-CL-309) trial. The trial results showed a statistically-significant and clinically-meaningful improvement in PFS with the BTK inhibitor as monotherapy in comparison to the combination of rituximab plus physician’s choice of idelalisib or bendamustine.
Calquence has approval for the treatment of relapsed or refractory mantle cell lymphoma (MCL) in adult patients in the US, Brazil, the UAE, and Qatar.
The drug works by binding covalently to BTK, thereby blocking its activity. In B-cells, BTK signalling leads to activation of pathways required for B-cell proliferation, trafficking, chemotaxis, and adhesion.
The BTK inhibitor is also being developed for the treatment of diffuse large B-cell lymphoma, Waldenstrom macroglobulinaemia, multiple myeloma, follicular lymphoma and other haematologic malignancies.