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Phase II, randomized, open-label study of durvalumab (MEDI4736) or tremelimumab monotherapy, or durvalumab + tremelimumab, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CONDOR

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P152

https://doi.org/10.1186/2051-1426-3-S2-P152

  • Published:

Keywords

  • Inhibitory Immune Checkpoint
  • Synergistic Antitumor Effect
  • Promising Antitumor Activity
  • Manageable Safety Profile
  • Independent Central Review

Background

First-line palliative treatment for patients with R/M SCCHN includes platinum-based chemotherapy. There are no standard second-line options upon relapse and median survival is limited. In SCCHN, tumors create a highly immunosuppressive environment and evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) axis, making immunotherapy an attractive option to study in this disease. Durvalumab (MEDI4736) is a selective, high affinity human IgG1 mAb that blocks PD-L1 binding to PD-1 (IC50 0.1 nM) and CD80 (IC50 0.04 nM) that has shown promising antitumor activity in the SCCHN cohort of a Phase I/II study (NCT01693562). Tremelimumab is a selective human IgG2 mAb inhibitor of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) that has been combined with durvalumab in a Phase Ib study in patients with NSCLC (NCT02000947), with encouraging clinical activity and a manageable safety profile. While anti-PD-1/PD-L1 monotherapy may be associated with greater clinical benefit in patients with PD-L1+ tumors, combination therapy has clinical activity in both PD-L1+ and PD-L1 patients in several solid tumors, enhancing the antitumor activity of anti-PD-1/PD-L1 agents in patients with PD-L1 tumors. The PD-L1 and CTLA-4 pathways are non-redundant and preclinical data indicate targeting both may induce synergistic antitumor effects. Here we describe the CONDOR study (NCT02319044), a Phase II study to determine the efficacy and safety of durvalumab monotherapy, tremelimumab monotherapy, and their combination in PD-L1 R/M SCCHN patients who have failed prior platinumtherapy.

Methods

This is a randomized, open-label, multicenter, global, Phase II study in immunotherapy-naïve patients with PD-L1 R/M SCCHN who have progressed during or after treatment with a platinum-containing regimen for R/M disease. Patients with tumoral PD-L1 expression below a pre-specified cut-off level of < 25% tumor cells with membrane staining, as determined by an immunohistochemistry assay, are deemed PD-L1. Patients (N=240) will be randomized 1:1:2 to receive durvalumab (10 mg/kg IV) monotherapy; tremelimumab (10 mg/kg IV) monotherapy; or durvalumab (20 mg/kg IV) plus tremelimumab (1 mg/kg IV) combination therapy for up to 12 months (Figure 1). Stratification factors include human papillomavirus (HPV) and smoking history. The primary endpoint is objective response rate (ORR; RECIST v1.1), based on independent central review. Secondary endpoints will further assess disease control rate, duration of response, progression-free survival, and overall survival; safety (CTCAE v4.03) and tolerability; and health-related quality of life. Exploratory outcomes include pharmacokinetics, immunogenicity, and potential biomarkers of response to treatment. Recruitment is ongoing.

Trial registration

ClinicalTrials.gov identifier NCT02319044.

Authors’ Affiliations

(1)
Vanderbilt University, Nashville, TN, USA
(2)
Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France
(3)
Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK
(4)
Centre Léon Bérard, University of Lyon, Lyon, France
(5)
AstraZeneca, Gaithersburg, MD, USA
(6)
Princess Margaret Cancer Centre, Toronto, ON, Canada

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