There are limited treatment options for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) who discontinue treatment with ibrutinib due to disease progression, transformation, or intolerance, and these patients have a very poor prognosis. In a phase 1 study, the Fc-enhanced, humanized, CD19 antibody MOR208 showed promising activity in patients with R/R CLL/small lymphocytic lymphoma (SLL). Furthermore, preclinical models suggest that the clinical activity of MOR208 may be complementary to idelalisib (an inhibitor of PI3Kδ) and venetoclax (an inhibitor of BCL-2), both approved for the treatment of CLL.
To evaluate the efficacy and safety of MOR208 combined with idelalisib or venetoclax, investigators initiated a 2-cohort, phase 2 study in adult patients with R/R CLL/SLL. To be included in the study, patients were required to receive prior treatment or demonstrate intolerance to treatment with a Bruton’s tyrosine kinase inhibitor, have Eastern Cooperative Oncology Group performance status of 0 to 2, and maintain adequate organ function.
Each study cohort is expected to include 120 patients. Patients will be treated with intravenous MOR208 12 mg/kg (weekly for the first 3 months, every second week for the next 3 months, and monthly thereafter) in combination with oral idelalisib 150 mg twice daily or venetoclax administered on a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. Treatment will continue for a maximum of 24 cycles or until disease progression. The primary end point is overall response rate based on independent review. Secondary and exploratory end points include progression-free survival and overall survival, time to progression, duration of response, safety, MOR208 immunogenicity and pharmacokinetics, quality of life, and minimal residual disease negativity. The study is expected to shed light on potential treatment options in a difficult-to-treat population of patients with R/R CLL and R/R SLL.
Wendtner CM, et al. ASCO Abstract TPS7567.