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 Masárová, Ghayas C. Issa, Guillermo Montalban‐Bravo, Michael Andreeff, Jan A. Burger, Darla Miller, Lynette Alexander, Aung Naing, Guillermo Garcia‐Manero, Farhad Ravandi, Naval Daver
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.