TY - JOUR
T1 - Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
AU - Ravandi, Farhad
AU - Bashey, Asad
AU - Foran, James
AU - Stock, Wendy
AU - Mawad, Raya
AU - Short, Nicholas
AU - Yilmaz, Musa
AU - Kantarjian, Hagop
AU - Odenike, Olatoyosi
AU - Patel, Anand
AU - Garcha, Raman
AU - Ainsworth, William Barrett
AU - Clynes, Raphael
AU - Kanodia, Jitendra
AU - Ding, Ying
AU - Li, Huajiang
AU - Kye, Steve
AU - Mims, Alice
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology.
PY - 2023/10/29
Y1 - 2023/10/29
N2 - Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.
AB - Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.
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U2 - 10.1182/bloodadvances.2023010956
DO - 10.1182/bloodadvances.2023010956
M3 - Article
C2 - 37647601
AN - SCOPUS:85176788059
SN - 2473-9529
VL - 7
SP - 6492
EP - 6505
JO - Blood Advances
JF - Blood Advances
IS - 21
ER -