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Developmental therapeutics

1671 - Anti-oxidized macrophage migration inhibitory factor (oxMIF) antibody imalumab (BAX69) in advanced solid tumors: Final results of first-in-human phase 1 study


09 Oct 2016


Developmental therapeutics


Devalingam Mahalingam


Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368


D. Mahalingam1, M.R. Patel2, J.C. Sachdev3, L.L. Hart4, N. Halama5, R.K. Ramanathan6, J. Sarantopoulos7, X. Liu8, S. Yazji8, D. Jäger5, M. Yoon8, G.Ç. Manzur8, D. Adib8, R. Kerschbaumer9, A. Tsimberidou10

Author affiliations

  • 1 Hematology/oncology, Cancer Therapy Research Center, 78229 - San Antonio/US
  • 2 Sarah Cannon Research Institute, Florida Cancer Specialists, 34232 - Sarasota/US
  • 3 Oncology, HonorHealth Research Institute, 85258 - Scottsdale/US
  • 4 Hematology/oncology, Florida Cancer Specialists, 33905 - Ft. Myers/US
  • 5 Oncology, National Center for Tumor Diseases, 69120 - Heidelberg/DE
  • 6 Hematology/oncology, Mayo Clinic Cancer Center, 85259 - Scottsdale/US
  • 7 Oncology, Institute for Drug Development Cancer Therapy Research Center, 78229 - San Antonio/US
  • 8 Clinical, Baxalta, 02142 - Cambridge/US
  • 9 Clinical, Baxalta Innovations GmbH, 113291 - Vienna/AT
  • 10 Investigational Cancer Therapeutics, MD Anderson Cancer Center, 77030 - Houston/US


Abstract 1671


MIF is a pleiotropic cytokine involved in tumor cell proliferation, angiogenesis, and inflammation. oxMIF is the pathogenic isoform found in tumor and its stroma. Imalumab is a novel recombinant, fully human, monoclonal antibody that targets oxMIF, with antitumor activity.


Dose escalation study (3 + 3 design). Primary endpoint was maximum tolerated dose (MTD). Secondary endpoints were antitumor activity, safety, pharmacokinetics (PK), and pharmacodynamics (PD). Patients (pts), previously treated with other agents, received intravenous (IV) imalumab [28-d cycles; 2 dose schedules]: biweekly in all solid tumors (Q2W); weekly in metastatic colorectal cancer (mCRC), metastatic ovarian cancer (OvCa), and metastatic non-small cell lung cancer (NSCLC) (QW).


50 pts dosed on the trial: 19 (Q2W) in 6 cohorts (1, 3, 10, 25, 37.5, and 50 mg/kg), and 31 (QW) in 2 cohorts (10 and 25 mg/kg) including expansion (10 mg/kg) into mCRC, OvCa, and NSCLC. Dose escalation was stopped at 50 mg/kg (Q2W) and 25 mg/kg (QW). MTD was not reached. One mCRC pt reported dose-limiting toxicities: hypersensitivity pneumonitis (Q2W; 50 mg/kg) at grade 3. One NSCLC pt had grade 3 treatment-related AEs (TRAE): constipation, nausea, and vomiting. Grade 2 TRAEs included: fatigue (n = 2), diarrhea (n = 1), peripheral edema (n = 1), infusion reaction (n = 1), and urticaria (n = 1). Stable disease (SD) ≥4 mo was seen in 8 pts, including 1 pt with NSCLC who achieved SD for 12.6 mo and 1 with OvCa ongoing beyond 10 mo. In DS2, pre- and on-therapy tumor biopsies showed tissue penetration of imalumab resulting in target saturation in all biopsy-evaluable patients in all 3 tumor types. Biopsies revealed regulation of PI3K-AKT-mTOR downstream signaling, TNF-α signaling, anti-inflammatory cytokines (IL-1 and IL-10), and apoptosis. Based on clinical PK and PD study, 10 mg/kg weekly was considered a biologically active dose and sufficient to reach ≥95% target binding by the end of first cycle.


Imalumab 10 mg/kg IV weekly was well tolerated and showed single-agent antitumor activity in these pts.

Clinical trial identification


Legal entity responsible for the study





D. Mahalingam: Participated in Ad Boards: Baxter, Genspera, Dendreon, Sanofi, Celgene. X. Liu, S. Yazji, M. Yoon, G.Ç. Manzur, D. Adib: Employee of Baxalta. R. Kerschbaumer: Employee of Celgene A. Tsimberidou: Grants/Research Support Recipient: Onyx, EMD Serono, Baxter, Foundation Medicine All other authors have declared no conflicts of interest.

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