SITC 2018: FURTHER ANALYSES OF THE PHASE II STUDY OF THE COMBINATION OF MONALIZUMAB AND CETUXIMAB IN HEAD AND NECK PATIENTS SHOW ENCOURAGING SURVIVAL DATA IN BOTH SUBGROUPS OF IO-NAÏVE AND IO-PRETREATED SCCHN PATIENTS
- These data support the advancement of the clinical program, starting with the enrollment of an additional cohort of patients who received both prior platinum-based chemotherapy and PD-1/L1 inhibitors ("IO-pretreated")
- An oral presentation took place on Sunday, November 11, at the SITC 2018 Annual Meeting in Washington, D.C., USA, by Professor Roger B. Cohen, Prof. of Medicine at the Hospital of the University of Pennsylvania and Principal Investigator of the study
Marseille, France, November 12, 2018, 7:00 AM CET
Innate Pharma SA (the "Company" - Euronext Paris: FR0010331421 - IPH), today announced exploratory subgroup analyses and preliminary translational data from the Phase II trial evaluating the combination of monalizumab and cetuximab (anti-EGFR) in previously treated patients with recurrent and/or metastatic squamous cell carcinoma of the head & neck (R/M SCCHN). Monalizumab is a first-in-class checkpoint inhibitor targeting NKG2A inhibitory receptors expressed on tumor-infiltrating cytotoxic CD8 T lymphocytes and NK cells.
"The subgroup analysis revealed very interesting durable responses in both IO-naïve and IO-pretreated patients," commented Pierre Dodion, Chief Medical Officer of Innate Pharma. "Patients who have failed on IO-therapy currently have no other treatment option. The fact that they appear to benefit with prolonged survival is rather remarkable and prompted us to advance our clinical program. Discussions are taking place in parallel with regards to the next steps in IO naïve patients".
"The high disease control rate that we observed in this study along with the favorable trends in progression-free and overall survival, including a preliminary estimate of median overall survival of 10.3 months, are very encouraging," commented Professor Roger B. Cohen, Principal Investigator of the study. "We also saw evidence of clinical activity in both IO-naive and IO-pretreated patients. If confirmed, these data would provide support for a highly novel immunotherapeutic combination with a unique mechanism of action for the treatment of patients with head & neck cancer."
Data from the cohort of 40 patients were reported at 2018 ESMO congress in October. Exploratory subgroup analysis revealed encouraging responses, durability of response, PFS and OS in IO-naïve and IO-pretreated patients.
|Cut-off August 31, 2018|| All patients|
|ORR [95% CI]||27.5% [16-43]||35% [19-55]||18% [6-41]|
|Median PFS [95% CI]||5.0 m [3.7-6.9]||4.0 m[3.7-10.6]||5.0 m [3.5-NR]|
|Median OS [95% CI]||10.3 m [7.3-NR]||10.3 m [7.2-NR]||12.8 m [6.0-NR]|
|DCR 24 weeks||35% [22-51]||39% [22-59]||29% [13-53]|
|Median time to response [range]||1.6 m [1.5-3.9]||1.7 m [1.5-3.9]||1.6 m [1.6-3.1]|
|Median duration of response [95% CI]||5.6 m [3.8-NR]||5.3 m [3.8-NR]||5.6 m [3.7-NR]|
Eric Vivier, Chief Scientific Officer of Innate Pharma, said: "We are combining the use of state-of-the-art technologies including high-dimensional flow cytometry, single cell RNA seq and computational pathology, to monitor the immune response in patients. Data support the mode of action of monalizumab as unleashing a multilayered immune response involving both NK and T cells. As such, monalizumab appears as a first-in-class second generation immune checkpoint inhibitor with a large spectrum of immune targets. He added: "While preliminary, translational results suggest that the combination of monalizumab and cetuximab is associated with a reshaping of "cold tumors" into "hot tumors" prone to sustain tumor immunity".
Preliminary biomarker analysis show indeed that while the combination did not impair the distribution or absolute counts of peripheral NKG2A+ NK and CD8+ T cells, an infiltration of NK cells and CD8+T cells is detected very early upon treatment (day 15) at the tumor bed. Further, tumor-infiltrating NK and CD8+ T cells may be predictive of RECIST response, tumor reduction and PFS.
Importantly, the activity of the monalizumab and cetuximab combination appears to occur across HPV status, tumor burden and PD-L1 expression.
The presentation is available in the monalizumab section on Innate Pharma's website.
Monalizumab is a first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8 T lymphocytes and NK cells.
NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently up-regulated on cancer cells of many solid tumors and hematological malignancies. Hence, monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells. Monalizumab may also enhance the cytotoxic potential of other therapeutic antibodies.
AstraZeneca and MedImmune, AstraZeneca's global biologics research and development arm, obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The companies currently share Phase II development for monalizumab in a broad exploratory clinical program focused on investigating monalizumab in combination strategies.
Cetuximab is an anti-EGFR monoclonal antibody blocking oncogenic signaling and inducing Fcy receptor-mediated antibody dependent cellular cytotoxicity (ADCC). NK cells mediate cetuximab-induced ADCC against SCCHN; genetic and preclinical experiments suggest that ADCC can be enhanced by NK-stimulators.
The activity of cetuximab single agent in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is limited with a 12.6% ORR, a median PFS of 2.3 months and a median OS of 5.6 months (Vermorken et al, JCO 2007).
About Innate Pharma:
Innate Pharma S.A. is a fully integrated oncology-focused biotech company dedicated to improving treatment and clinical outcomes for patients through therapeutic antibodies that harness the immune system to fight cancer.
Innate Pharma's commercial-stage product, Lumoxiti, in-licensed from AstraZeneca, was approved by the FDA in September 2018. Lumoxiti is a first-in class specialty oncology product for hairy cell leukemia (HCL). Innate Pharma's broad pipeline of antibodies includes several first-in-class clinical and preclinical candidates in cancers with high unmet medical need.
Innate Pharma has pioneered the discovery and development of checkpoint inhibitors, with a unique expertise and understanding of Natural Killer cell biology. This innovative approach has resulted in major alliances with leaders in the biopharmaceutical industry including Bristol-Myers Squibb, Novo Nordisk A/S, Sanofi, and a landmark and multi-products partnership with
Based in Marseille, France, Innate Pharma is listed on Euronext Paris.
Learn more about Innate Pharma at www.innate-pharma.com
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This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website www.amf-france.org or on Innate Pharma's website.
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