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-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.

Keywords:

• Monoclonal antibody
• gemtuzumab ozogamicin
• venetoclax
• azacitidine
• avelumab

Acknowledgments

This study was conducted as a collaboration between UTMDACC and Pfizer. UTMDACC was the study sponsor.

Author contributions

N.J.S. and N.D. designed the study, enrolled patients, analyzed the data wrote the first version of the manuscript. G.B., N.P., C.D.D., E.J., F.R., M.K., Y.A., K.S., K.T., Z.E., L.M., T.M.K., G.G-M., E.J., G.C.I. G.M-B., A.N., M.A., J.A.B. and H.K. enrolled patients. J.N. and J.M. designed the study and performed statistical analysis, W.M. analyzed the data, D.M. and L.A. supervised the study and enrolled patients. All authors critically reviewed and approved the manuscript.

Disclosure statement

N.J.S. has served as consultant for Takeda Oncology and AstraZeneca, reports receiving research grants from Takeda Oncology and Astellas Pharma Inc., and has received honoraria from Amgen. A.N. has received research funding from NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor/Millendo, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, ImmuneOncia, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven & Eight Biopharma, and SOTIO Biotech AG and has served in an advisory role for CytomX Therapeutics, Novartis, Genome & Company, OncoSec KEYNOTE-695, Kymab, STCube Pharmaceuticals, and Deka Biosciences. N.D. has received research funding from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, Gilead, Sevier, Genentech, Astellas, Daiichi-Sankyo, Abbvie, Hanmi, Trovagene, FATE therapeutics, Amgen, Novimmune, Glycomimetics, Trillium, and ImmunoGen and has served in a consulting or advisory role for Daiichi-Sankyo, Bristol-Myers Squibb, Arog, Pfizer, Novartis, Jazz, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen, Shattuck labs, and Agios. The other authors report no relevant conflicts of interest.

Additional information

Funding

This study was sponsored by MD Anderson Cancer Center. It was conducted in collaboration with Pfizer, which provided research funding and free drug as part of an alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany. This research was also supported by an MD Anderson Cancer Center Support Grant [CA016672] and SPORE. N.J.S. is supported by the K12 Paul Calabresi Clinical Oncology Scholar Award and the American Society of Hematology Junior Faculty Scholar Award in Clinical Research. N.D. is supported by the Dick Clark Immunotherapy Fund and the MD Anderson Cancer Center Faculty Scholar Award.