Bristol-Myers Squibb (BMY), Innate Pharma SA Announce Encouraging Data from lirilumab and Opdivo Phase 1/2 in SCCHN Cohort

November 14, 2016 6:26 AM EST

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Bristol-Myers Squibb Company (NYSE: BMY) and Innate Pharma SA announced an interim efficacy analysis from a Phase 1/2 study of the combination of lirilumab and Opdivo (nivolumab) in the cohort of advanced platinum refractory squamous cell carcinoma of the head and neck (SCCHN), including exploratory biomarker analyses of patient response by level of PD-L1 expression. Among 29 evaluable patients with SCCHN, the objective response rate (ORR), 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 ORR of 41% (7/17) in patients with ≥1% PD-L1 expression.

Lirilumab is directed against the inhibitory killer-cell immunoglobulin-like receptors (KIRs) expressed predominantly on natural killer (NK) cells, which belong to the innate immune system, while Opdivo blocks the inhibitory function of the 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, and were presented at a late-breaking oral presentation (abstract 456) at the Society for Immunotherapy of Cancer (SITC) 31 Annual Meeting on November 12 at 11:15 a.m. EST in National Harbor, Maryland. Preliminary efficacy and exploratory biomarker analyses of patient response by biomarker subgroups were presented.

The safety profile associated with lirilumab in combination with Opdivo was generally consistent with that observed with Opdivo monotherapy. The overall rate of treatment-related adverse events (TRAEs) was reported as 72% (114/159) and the rate of Grade 3-4 TRAEs was 15% (24/159). Discontinuations due to TRAEs 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 Opdivo, respectively, may provide enhanced clinical activity, particularly in PD-L1 positive tumors, with deep and durable responses in some patients," said Rom Leidner, 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.”

“The preliminary signals of anti-tumor activity we are seeing with the combination of lirilumab and Opdivo in head and neck cancer patients compare favorably to data previously presented on Opdivo monotherapy in a similar patient population. We are encouraged by the suggestion of enhanced benefit, particularly in inflamed tumors as defined by increasing PD-L1 expression," said Tim Reilly, head of Oncology Early Assets Development at Bristol-Myers Squibb. "We aim to apply what we have been learning about these complementary mechanisms and biomarker subgroups to maximize the potential clinical benefit of lirilumab and Opdivo across a range of tumor types and are excited about continuing to expand our study of Opdivo with complementary pathways.”

“We are very encouraged by these interim efficacy data and are eagerly awaiting the next steps of the clinical development of the combination of lirilumab and Opdivo” said Pierre Dodion, Chief Medical Officer of Innate Pharma. “These clinical data constitute crucial progress that validates our pioneering work on the role of innate immunity and NK cells in cancer. They support our ambition to be at the forefront of developing novel combination immunotherapies.”

About CA223-001: A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors

CA223-001 is a Phase 1/2 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 ≥ 1 prior therapy received lirilumab 0.1–3.0 mg/kg once every 4 weeks (Q4W) plus nivolumab 3.0 mg/kg Q2W. Cohort expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg Q4W plus nivolumab 3.0 mg/kg Q2W in patients with advanced solid tumors. The data reported at SITC pertain to an expansion cohort in SCCHN. Key study endpoints include safety (primary), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and biomarker assessments.

The purpose of this Phase 1/2 open label study is to determine the safety of the combination of lirilumab and nivolumab and to explore the preliminary anti-tumor activity of the combination in patients with a range of advanced solid tumors.

About Lirilumab (IPH2102/BMS-986015):

Lirilumab is a fully human monoclonal antibody that is designed to act as a checkpoint inhibitor by blocking the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands. Blocking these receptors facilitates activation of NK cells and potentially some subsets of T cells, ultimately leading to destruction of tumor cells.

Lirilumab is licensed to Bristol-Myers Squibb Company. As part of the agreement with Innate Pharma, Bristol-Myers Squibb holds exclusive worldwide rights to develop, manufacture and commercialize lirilumab and related compounds blocking KIR receptors, for all indications. Under the agreement, Innate Pharma conducts the development of lirilumab through Phase 2 in acute myeloid leukemia (“AML”).

Innate Pharma is currently testing lirilumab in a randomized, double-blind, placebo-controlled Phase 2 trial as maintenance treatment in elderly patients with AML in first complete remission (“EffiKIR” trial). In addition, lirilumab is also being evaluated by Bristol-Myers Squibb in clinical trials in combination with other agents in a variety of tumor types.

About Head & Neck Cancer

Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers with global incidence expected to increase by 17% between 2012 and 2022. Risk factors for SCCHN include tobacco and alcohol consumption. The Human Papilloma Virus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America. Quality of life is often impacted for SCCHN patients, as physiological function (breathing, swallowing, eating, drinking), personal characteristics (appearance, speaking, voice), sensory function (taste, smell, hearing), and psychological/social function can be affected.

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