1072P - A Phase 1 first-in-human study of MEDI0680, an anti-PD-1 monoclonal antibody (mAb) in adult patients (pts) with advanced tumors

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Presenter Aung Naing
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors A. Naing1, S. Goel2, B. Curti3, A. Weise4, J.P. Eder5, S. Marshall6, C. Morehouse7, X. Li8, J.J. Karakunnel6, J. Infante9
  • 1Department Of Investigational Cancer Therapeutics, MD Anderson Cancer Center, TX 77030 - Houston/US
  • 2Department Of Medical Oncology, Montefiore Medical Park at Eastchester, New York/US
  • 3Department Of Medical Oncology, Providence Cancer Center and Earle A. Chiles Research Institute, Portland/US
  • 4Department Of Oncology, Karmanos Cancer Center, Detroit/US
  • 5Yale School Of Medicine, Yale Cancer Center, New Haven/US
  • 6Clinical Development, MedImmune, Gaithersburg/US
  • 7Translational Medicine, MedImmune, Gaithersburg/US
  • 8Biostatistics, MedImmune, Gaithersburg/US
  • 9Phase I Drug Development Unit, Sarah Cannon Research Institute/ Tennessee Oncology, PLLC, Nashville/US



Programmed cell death-1 (PD-1) inhibits T-cell activation. Blocking the PD-1/programmed cell death ligand 1/2 (PD-L1/2) axis has an acceptable safety profile, induces antitumor responses, and provides clinical benefit across tumors. MEDI0680 is a humanized IgG4κ mAb specific for human PD-1 that blocks interaction with PD-L1/2.


This is an ongoing Phase 1, multicenter, open-label, first-in-human, dose-escalation and expansion study of single-agent MEDI0680 in immunotherapy-naïve pts with advanced solid tumors. Primary objectives are safety/tolerability and maximum tolerated dose (MTD). Secondary objectives include pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity (modified RECIST v1.1).


As of 2 Nov 2015, 58 pts have enrolled across 9 cohorts (0.1–20 mg/kg given Q3W, Q2W, QWx2 then Q2W, or QWx4 then Q2W). MTD was not reached. Treatment-related AEs occurred in 46 pts; most common (>10%) were fatigue (21%), nausea (14%) and arthralgia (14%). Related Grade 3/4 AEs occurred in 10 pts; most common (>1 pt) were anemia, arthralgia and increased AST (3% each). 2 pts discontinued due to related AEs: pyrexia in 1 pt; and increased AST, myasthenia gravis and myositis in 1 pt. There were no Grade 5 related AEs. MEDI0680 had a linear PK profile with dose-proportional increases in peak serum concentration. Median PD-1 receptor occupancy on CD3+ T cells was ≥70% after 1 cycle of 10 or 20 mg/kg Q2W. Increased percentages of Ki67 + , ICOS+ and HLA-DR+ T cells; increased levels of plasma IFNɣ; and enhanced intra-tumor gene expression for these factors were seen after treatment, demonstrating biological activity of MEDI0680. Of 51 evaluable pts, 9 (18%) had an objective response (8 had renal cancer or melanoma), including 1 (2%) complete response (renal cancer). 14 (28%) pts had stable disease as their best response. The recommended dose is 20 mg/kg Q2W, based on PK, PD, safety and efficacy.


MEDI0680 has an acceptable safety profile, with preliminary signs of efficacy. A Phase 1 combination study with durvalumab to test the concept of complete PD-1/PD-L1 axis blockade is ongoing in advanced solid tumors.

Clinical trial identification

NCT02013804 (release date: December 12, 2013)

Legal entity responsible for the study





A. Naing: Research funding: NCI; EMD Serono; Medimmune; Healios Onc. Nutrition, ATTEROCOR; Amplimmune; ARMO BioSciences; Karyopharm Therapeutics; Incyte; Novartis. B. Curti: Honoraria: Prometheus Speaker Bureau: Prometheus Research funding: Prometheus, Viralytics, Galectin Therapeutics Travel, accommodation, expenses: BMS, Medimmune, AgonOx, Prometheus. J.P. Eder: Honoraria: Merck. S. Marshall: Employment and stock options: Medimmune, Amplimmune. C. Morehouse: Employment: Medimmune Stock/ownership: Medimmune (AstraZeneca). X. Li: Employment: MedImmune. J.J. Karakunnel: Employee of MedImmune and own stock or options in AstraZeneca. Also an employee of MedStar Montgomery Medical Center and Fauquier Hospital. J. Infante: Consulting/advisory: MedImmune Research funding: MedImmune. All other authors have declared no conflicts of interest.