Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody: A phase 1, open-label study in advanced malignancies


10 Oct 2016


Immunotherapy of cancer


Omid Hamid


Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378


O. Hamid1, L.Q. Chow2, R.E. Sanborn3, S. Marshall4, C. Black5, M. Gribbin6, J. McDevitt4, J.J. Karakunnel4, J.E. Gray7

Author affiliations

  • 1 Melanoma Therapeutics, The Angeles Clinic and Research Institute, CA 90025 - Los Angeles/US
  • 2 Department Of Medicine, Division Of Medical Oncology, University of Washington, Seattle/US
  • 3 Department Of Medical Oncology, Earle A. Chiles Research Institute, Providence Cancer Center, Portland/US
  • 4 Clinical Development, MedImmune, Gaithersburg/US
  • 5 Translational Medicine, MedImmune, Gaithersburg/US
  • 6 Biostatistics, MedImmune, Gaithersburg/US
  • 7 Department Of Thoracic Oncology, Moffitt Cancer Center and Research Institute, Tampa/US



The PD-1/PD-L1 pathway is a key regulator of T-cell activation and a promising target for cancer treatment. MEDI0680 (M) is a humanized IgG4κ mAb specific for human PD-1 that blocks interaction with PD-L1 and programmed cell death ligand-2 (PD-L2). Durvalumab (D; MEDI4736) is a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Blocking both the PD-1 receptor and its ligand by combining M + D offers the potential for complete PD-1/PD-L1 axis inhibition.


This ongoing Phase 1 open-label, dose-escalation and expansion study is evaluating M + D in patients (pts) ≥18 years with relapsed/refractory advanced solid malignancies and ECOG performance status 0-1 (NCT02118337). The primary objectives are safety and maximum tolerated dose (MTD). Secondary objectives include antitumor activity.


As of 2 November 2015, 30 pts across various histologies were treated in 6 dose cohorts (Table) with 50% remaining on study. 1 dose-limiting toxicity occurred (Cohort 5; Grade 3 elevated AST/ALT). The MTD has not been reached. The most common drug-related AEs were pruritus (17%); diarrhea and fatigue (both 13%); and flushing, peripheral edema, and pyrexia (each 10%). Immune-related AEs were similar to those seen with other checkpoint blockade agents. No drug-related AEs led to death. 2 pts (7%) discontinued due to drug-related AEs. Of 26 evaluable pts, 1 had a complete response (CR; Cohort 5; bladder cancer), 3 had a partial response (PR) and 9 had stable disease (SD). Increased Ki67+ (proliferating) CD4+ and CD8+ T cells and elevated circulating IFNɣ, CXCL9, CXCL10, and CXCL11 levels were observed with M + D, indicating pharmacodynamic activity of PD-1/PD-L1 pathway blockade. Updated clinical data will be presented.

Cohort 1 2 3 4 5 6 Total
Dose every 2 weeks (Q2W) (mg/kg), M + D 0.1 + 3 0.1 + 10 0.5 + 10 2.5 + 10 10 + 10 20 + 10
N 4 5 3 3 9 6 30
Patients with drug-related AEs, n (%)
All grades 2 (50) 3 (60) 3 (100) 2 (67) 8 (89) 3 (50) 21 (70)
Grade ≥3 1 (25) 0 1 (33) 0 3 (33) 0 5 (17)
All grades leading to discontinuation 1 (25) 1 (20) 1 (33) 1 (33) 2 (22) 0 6 (20)
Objective response rate (CR + PR), n/N (%) 1/4 (25) 0 0 0 3/8 (38) 0 4/26 (15)
Disease control (CR + PR + SD ≥8 weeks), n/N (%) 2/4 (50) 1/5 (20) 1/3 (33) 0 5/8 (63) 0 9/26 (35)

*Response evaluable population


M 10 mg/kg + D 10 mg/kg Q2W appears to be well-tolerated and active in this population.

Clinical trial identification


Legal entity responsible for the study





O. Hamid: Consulting/Advisory: Merck, Merck Serono, Pfizer, Amgen, Novartis, Roche, BMS, Genentech Speakers Bureau: BMS, Genentech, Novartis Research funding: None. L.Q. Chow: Honoraria: Astellas Consulting/Advisory: Novartis, Amgen, Emergent Research funding: Novartis, BMS, Eli Lilly/Imclone Advisory board; travel & accommodations/Research funding: Merck. R.E. Sanborn: Consulting/Advisory: Amgen Research funding: BMS, Medimmune. S. Marshall: Employment: MedImmune, Amplimmune Stock options: MedImmune. C. Black: Employment: MedImmune Stock/ownership: AZ. M. Gribbin: Employment: Medimmune Stock ownership: MedImmune. J. McDevitt: Employment: MedImmune Stock/ownership: MedImmune (AZ). J.J. Karakunnel: Employee of MedImmune and own stock or options in AstraZeneca. JJK is also an employee of MedStar Montgomery Medical Center and Fauquier Hospital. J.E. Gray: Consulting/Advisory: AZ Travel, accommodation, expenses: AZ.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings