Clinical lymphoma, myeloma & leukemia · 2026
A Phase I Study of Copanlisib and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Crombie Jennifer L, Kim Austin I, Redd Robert, Bartlett Nancy, Patterson Victoria, Carey Celeste, Balasubramanian Sobana, Odejide Oreofe, Merryman Reid W, LaCasce Ann, Jacobson Caron A, Jacobsen Eric, Parry Erin, Fisher David, Herrera Alex, Davids Matthew S, Shipp Margaret, Armand Philippe, Shouse Geoffrey
Аннотация
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.
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.