A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia

Nicholas J. Short; Gautam Borthakur; Naveen Pemmaraju; Courtney D. Dinardo; Tapan M. Kadia; Elias Jabbour; Marina Konopleva; Walid Macaron; Jing Ning; Junsheng Ma; Sherry Pierce; Yesid Alvarado; Koji Sasaki; Koichi Takahashi; Zeev Estrov; Lucia Masarova; Ghayas C. Issa; Guillermo Montalban-Bravo; Michael Andreeff; Jan A. Burger; Darla Miller; Lynette Alexander; Aung Naing; Guillermo Garcia-Manero; Farhad Ravandi; Naval Daver

doi:10.1080/10428194.2022.2062345

A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia

Nicholas J. Short
, Gautam Borthakur
, Naveen Pemmaraju
, Courtney D. Dinardo
, Tapan M. Kadia
, Elias Jabbour
, Marina Konopleva
, Walid Macaron
, Jing Ning
, Junsheng Ma
, Sherry Pierce
, Yesid Alvarado
, Koji Sasaki
, Koichi Takahashi
, Zeev Estrov
, Lucia Masarova
, Ghayas C. Issa
, Guillermo Montalban-Bravo
, Michael Andreeff
, Jan A. Burger

Darla Miller, Lynette Alexander, Aung Naing, Guillermo Garcia-Manero, Farhad Ravandi, Naval Daver

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.

Original language	English (US)
Pages (from-to)	2161-2170
Number of pages	10
Journal	Leukemia and Lymphoma
Volume	63
Issue number	9
DOIs	https://doi.org/10.1080/10428194.2022.2062345
State	Published - 2022

Keywords

avelumab
azacitidine
gemtuzumab ozogamicin
Monoclonal antibody
venetoclax

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group
Flow Cytometry and Cellular Imaging Facility

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10.1080/10428194.2022.2062345

Cite this

Short, N. J., Borthakur, G., Pemmaraju, N., Dinardo, C. D., Kadia, T. M., Jabbour, E., Konopleva, M., Macaron, W., Ning, J., Ma, J., Pierce, S., Alvarado, Y., Sasaki, K., Takahashi, K., Estrov, Z., Masarova, L., Issa, G. C., Montalban-Bravo, G., Andreeff, M., ... Daver, N. (2022). A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia. Leukemia and Lymphoma, 63(9), 2161-2170. https://doi.org/10.1080/10428194.2022.2062345

Short, NJ, Borthakur, G, Pemmaraju, N , Dinardo, CD , Kadia, TM , Jabbour, E, Konopleva, M, Macaron, W, Ning, J, Ma, J, Pierce, S, Alvarado, Y, Sasaki, K, Takahashi, K, Estrov, Z, Masarova, L , Issa, GC , Montalban-Bravo, G , Andreeff, M , Burger, JA, Miller, D, Alexander, L, Naing, A , Garcia-Manero, G , Ravandi, F & Daver, N 2022, 'A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia', Leukemia and Lymphoma, vol. 63, no. 9, pp. 2161-2170. https://doi.org/10.1080/10428194.2022.2062345

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title = "A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia",

abstract = "We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-na{\"i}ve and prior venetoclax-exposed patients were 50\% and 22\%, respectively, and the 1-year OS rate was 31\%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.",

keywords = "avelumab, azacitidine, gemtuzumab ozogamicin, Monoclonal antibody, venetoclax",

author = "Short, \{Nicholas J.\} and Gautam Borthakur and Naveen Pemmaraju and Dinardo, \{Courtney D.\} and Kadia, \{Tapan M.\} and Elias Jabbour and Marina Konopleva and Walid Macaron and Jing Ning and Junsheng Ma and Sherry Pierce and Yesid Alvarado and Koji Sasaki and Koichi Takahashi and Zeev Estrov and Lucia Masarova and Issa, \{Ghayas C.\} and Guillermo Montalban-Bravo and Michael Andreeff and Burger, \{Jan A.\} and Darla Miller and Lynette Alexander and Aung Naing and Guillermo Garcia-Manero and Farhad Ravandi and Naval Daver",

note = "Publisher Copyright: {\textcopyright} 2022 Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2022",

doi = "10.1080/10428194.2022.2062345",

language = "English (US)",

volume = "63",

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T1 - A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia

AU - Short, Nicholas J.

AU - Borthakur, Gautam

AU - Pemmaraju, Naveen

AU - Dinardo, Courtney D.

AU - Kadia, Tapan M.

AU - Jabbour, Elias

AU - Konopleva, Marina

AU - Macaron, Walid

AU - Ning, Jing

AU - Ma, Junsheng

AU - Pierce, Sherry

AU - Alvarado, Yesid

AU - Sasaki, Koji

AU - Takahashi, Koichi

AU - Estrov, Zeev

AU - Masarova, Lucia

AU - Issa, Ghayas C.

AU - Montalban-Bravo, Guillermo

AU - Andreeff, Michael

AU - Burger, Jan A.

AU - Miller, Darla

AU - Alexander, Lynette

AU - Naing, Aung

AU - Garcia-Manero, Guillermo

AU - Ravandi, Farhad

AU - Daver, Naval

PY - 2022

Y1 - 2022

N2 - We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.

AB - We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.

KW - avelumab

KW - azacitidine

KW - gemtuzumab ozogamicin

KW - Monoclonal antibody

KW - venetoclax

UR - https://www.scopus.com/pages/publications/85129353584

UR - https://www.scopus.com/pages/publications/85129353584#tab=citedBy

U2 - 10.1080/10428194.2022.2062345

DO - 10.1080/10428194.2022.2062345

M3 - Article

C2 - 35442137

AN - SCOPUS:85129353584

SN - 1042-8194

VL - 63

SP - 2161

EP - 2170

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 9

ER -

A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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