- Monalizumab is a first-in-class broad-spectrum immune checkpoint inhibitor with a dual effect on both Natural Killer (NK) cells and T lymphocytes
- Monalizumab showed promising preclinical and clinical results in combination with durvalumab, another immune checkpoint inhibitor, and also in combination with cetuximab, a targeted therapy that notably enhances action of NK cells
Innate Pharma SA (the “Company” - Euronext Paris: FR0010331421 – IPH) today announced the publication of data demonstrating the potential of monalizumab, an anti-NKG2A antibody, which could extend cancer immunotherapies to NK cell-based treatments. Published in the prestigious journal Cell on November 29, 2018, this work, led by Professor Eric Vivier and the Innate Pharma teams in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca and renowned researchers and clinicians, will now be used as a reference for later development of monalizumab.
“With a dual effect on T cells and NK cells, monalizumab pioneers a new class of broad-spectrum immune checkpoint inhibitors,” said Eric Vivier, Chief Scientific Officer of Innate Pharma, Professor at Aix-Marseille University and lead author of this publication. “We hope monalizumab will soon offer a new therapeutic option to a diverse group of cancer patients based on the simultaneous blockade of two complementary inhibitory signals or the combination of inhibitory signal blockade with the delivery of an activating signal.”
Immune checkpoint inhibitors, in particular anti-PD-1/L1, have revolutionized cancer treatment over the past decade, providing long-lasting benefits. However, only a subset of patients respond favorably to PD-1/L1 blockade. The main current challenge of immuno-oncology is to overcome anti-PD-1/L1 resistance by targeting new immune checkpoints and cells and mastering therapeutic combinations.
“To deliver on the long-term potential of immunotherapy, we must find ways to augment anti-PD-1/L1 therapy to improve response rates in patients who have not responded to immune checkpoint therapies alone. We are encouraged to see these data provide a strong rationale for combinations with other immunotherapy antibodies, in particular our PD-L1 blocking antibody durvalumab,” added Ronald Herbst, VP Oncology Research at MedImmune. “We are continuing to explore the potential of monalizumab in combination with durvalumab in our ongoing phase II clinical trial, and hope to identify new ways of expanding the benefits of immunotherapy for patients with advanced solid tumors.”
This publication reports that monalizumab stimulates simultaneously the anti-tumor activity of NK cells and T cells by blocking the inhibitory receptor NKG2A. NKG2A is present at the surface of both cells within the tumor bed while its ligand, HLA-E, is frequently overexpressed in human tumors, thus opening a wide therapeutic window for monalizumab.
Importantly, the authors demonstrate that combination of their NKG2A blocking antibody with a PD-L1 blocking antibody provides an additive effect towards the activation of an anti-tumor immunity both in vitro and in tumor-bearing mice, setting the grounds for the use of monalizumab in combination immunotherapy and supporting the ongoing clinical trial evaluating monalizumab in combination with durvalumab in MSS-CRC* for which data were presented at the 2018 ASCO Annual Meeting. Another phase II clinical trial using monalizumab in combination with cetuximab (an antibody that blocks the EGFR** on tumor cells and induces ADCC by NK cells) in patients with head and neck cancer (SCCHN***), demonstrate that the monalizumab cetuximab combination is well tolerated and provides encouraging efficacy results. Results from this phase II trial were presented at the 2018 ESMO and SITC Annual Meetings.
* Microsatellite-stable colorectal cancer
** Epidermal Growth Factor Receptor
*** Squamous Cell Carcinoma of the Head and Neck