Date: 2017-11-22
Type of
information: Interim results
phase: 1-2
Announcement: interim results
Company: BMS (USA - NY) Innate Pharma (France)
Product: lirilumab or IPH2102/BMS-986015 in combination with nivolumab or Anti-PD-1 (BMS-936558)
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor. Lirilumab or IPH2102/BMS-986015 is a fully human monoclonal antibody blocking interaction between Killercell immunoglobulin-like receptors (KIR) on NK cells with their ligands. Blocking these receptors facilitates activation of NK cells and, potentially, destruction of tumor cells by the latter.
- Nivolumab or Anti-PD-1 is a fully-human antibody that targets the inhibitory receptor expressed on activated T-cells called PD-1 or programmed death-1. The two compounds are checkpoint inhibitors.
- IPH2102/BMS-986015 is licensed to BMS. As part of their agreement, BMS holds exclusive worldwide rights to develop, manufacture and commercialize IPH2102/BMS-986015 and related compounds blocking KIR receptors, for all indications. Under the agreement, Innate Pharma will conduct the development of IPH2102/BMS-986015 through Phase II in acute myeloid leukemia.
Disease: advanced refractory solid tumors, advanced platinum refractory squamous cell carcinoma of the head and neck (SCCHN)
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On November 22, 2017, Innate Pharma provided an
update on the clinical study program of lirilumab, licensed to BMS. While lirilumab was shown to be well-tolerated, the assessment of efficacy from the ongoing exploration of doublet combinations, notably the nivolumab combination in an extended population of SCCHN patients, did not provide clear evidence of benefit to patients or an obvious development path. Discussions are ongoing regarding next steps for the program.
Together with BMS, Innate Pharma will further examine these data to better understand the results and explore whether other combinations should be investigated.
- • On March 13, 2017, Innate Pharma announced that BMS has amended the clinical trial protocol for its ongoing
Phase I/II trial evaluating the safety and tolerability of lirilumab in combination with Opdivo® in patients with advanced refractory solid tumors. Under the amended protocol, the study will expand in scope to include additional cohorts of Opdivo® plus lirilumab in solid tumors, including a randomized cohort exploring Opdivo® with or without
lirilumab in platinum refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), and initial testing of the triplet combination of Opdivo®, Yervoy® and lirilumab in solid tumors. The protocol amendment follows the presentation at the Society for Immunotherapy of Cancer annual meeting (SITC, November 2016) of an interim efficacy analysis, which showed encouraging preliminary clinical benefit in the cohort of patients with advanced platinum refractory SCCHN in this Phase I/II trial.
- • On November 12, 2016, BMS and Innate Pharma 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. 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.
- • On November 8, 2016, Innate Pharma announced the publication of the late-breaking abstract on 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). The abstract is available on the Society for Immunotherapy of Cancer’s (SITC) website (Poster 456). In the abstract, data reports that among 29 evaluable patients with SCCHN, the objective response rate (ORR), as measured by Response Evaluation Criteria In Solid Tumors (RECIST), was 24 percent (n=7) and the disease control rate (DCR) was 52 percent (n=15). Seventeen percent (n=5) of these evaluable patients had deep responses, with reductions in tumor burden greater than 80 percent. Preliminary efficacy of lirilumab plus nivolumab in patients with advanced platinum-refractory SCCHN suggests clinical benefit with encouraging response rates and potential for deep and durable responses.
- 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.
Is
general: Yes
