SITC 2016: Interim Phase I/II Data Show Encouraging Clinical Benefit for Lirilumab in Combination With Nivolumab in Head and Neck Cancer

Key Points

  • Among 29 evaluable patients with squamous cell carcinoma of the head and neck, the objective response rate was 24% (n = 7).
  • 17% (n = 5) of these evaluable patients had deep responses, with reductions in tumor burden greater than 80%.
  • Early signals of enhanced clinical benefit were observed in PD-L1–positive tumors, with an objective response rate (ORR) of 41% (7/17) in patients with > 1% PD-L1 expression.

An interim efficacy analysis from a phase I/II study of the combination of lirilumab and nivolumab (Opdivo) in the cohort of advanced platinum refractory squamous cell carcinoma of the head and neck, including exploratory biomarker analyses of patient response by level of programmed death ligand 1 (PD-L1) expression, was presented at the Society for Immunotherapy of Cancer (SITC) 31st Annual Meeting in National Harbor, Maryland (Abstract 456).

Lirilumab is directed against the inhibitory killer-cell immunoglobulin-like receptors (KIR) expressed predominantly on natural killer (NK) cells, which belong to the innate immune system, while nivolumab blocks the inhibitory function of the programmed cell death 1 (PD-1) receptor on T cells. These data mark the first report of potential efficacy with an anti-KIR antibody in combination with an anti–PD-1 therapy. Preliminary efficacy and exploratory biomarker analyses of patient response by biomarker subgroups were presented.

Findings

Among 29 evaluable patients with squamous cell carcinoma of the head and neck, the objective response rate, a secondary endpoint measured by Response Evaluation Criteria in Solid Tumors (RECIST), was 24% (n = 7). Seventeen percent (n = 5) of these evaluable patients had deep responses, with reductions in tumor burden greater than 80%. Early signals of enhanced clinical benefit were observed in PD-L1–positive tumors, with an objective response rate of 41% (7/17) in patients with > 1% PD-L1 expression.

The safety profile associated with lirilumab in combination with nivolumab was generally consistent with that observed with nivolumab monotherapy. The overall rate of treatment-related adverse events was reported as 72% (114/159) and the rate of grade 3–4 treatment-related adverse events was 15% (24/159). Discontinuations due to treatment-related adverse events occurred in 8% of patients (12/159). These safety data were also reported at the 2016 European Society for Medical Oncology (ESMO) Congress.

“The interim efficacy results indicate that targeting both the KIR and PD-1 pathways with lirilumab and nivolumab, respectively, may provide enhanced clinical activity, particularly in PD-L1 positive tumors, with deep and durable responses in some patients,” said Rom Leidner, MD, Medical Oncologist, Earle A. Chiles Research Institute, Providence Cancer Center, and lead author of the study. “We look forward to continuing the study of this novel combination in patients with advanced platinum refractory squamous cell carcinoma of the head and neck, which is the seventh-leading cause of cancer globally.”

About CA223-001

CA223-001 is a phase I/II dose escalation and cohort expansion study of lirilumab in combination with nivolumab in 159 patients with advanced solid tumors. In this trial, patients received lirilumab (0.1, 0.3, 1.0, or 3.0 mg/kg) once every 4 weeks and nivolumab (3 mg/kg) once every 2 weeks.

During dose escalation, patients with advanced solid tumors who progressed after at least one prior therapy received lirilumab 0.1 to 3.0 mg/kg once every 4 weeks plus nivolumab 3.0 mg/kg once every 2 weeks. Cohort expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg once every 4 weeks plus nivolumab 3.0 mg/kg once every 2 weeks in patients with advanced solid tumors. The data reported at SITC pertain to an expansion cohort in squamous cell carcinoma of the head and neck. Key study endpoints include safety (primary), objective response rate, disease control rate, duration of response, and biomarker assessments.

This study was supported by Bristol-Myers Squibb Company and Innate Pharma SA.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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