A Phase I Study of Copanlisib and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND

Preclinical data support the combination of venetoclax and copanlisib in specific genomic subgroups of diffuse large B-cell lymphoma (DLBCL).

PATIENTS AND

METHODS

In this investigator-initiated, phase I, multicenter trial we aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of copanlisib and venetoclax in patients with relapsed/refractory (R/R) DLBCL. Key eligibility criteria included relapse after or noncandidate for autologous stem cell transplantation or chimeric antigen receptor T-cell therapy and adequate hematologic and organ function. Key exclusion criteria were poorly controlled hypertension or diabetes.

RESULTS

A total of 12 patients enrolled using a 3 + 3 design. The median age was 62 years (range 24-87 years) and 83% were male. The median number of prior treatments was 6 (range 1-11) and 10 patients had received prior CAR T-cell therapy. There were no dose limiting toxicities (DLT)s in dose level (DL)+2. Half of patients (2/4) in DL+3 were not able to escalate to 800 mg of venetoclax due to neutropenia and nonadherence. Key hematologic toxicities included neutropenia (50%, all grade (G) 3/4) and thrombocytopenia (42%, 17% ≥ G3), and the most common nonhematologic toxicities included nausea (33%, 8% ≥ G3), diarrhea (25%, all G1/2), elevated alkaline phosphatase (25%, 8% ≥ G3), fatigue (25%, all G1/2), and headache (25%, all G1/2). One patient had a complete response lasting 3 months. The median overall survival and progression-free survival were 4.1 and 1.6 months, respectively.

CONCLUSION

Although the combination was tolerable, efficacy was poor in this unselected, heavily pretreated population.