AstraZeneca Calls Off Monalizumab Study With Innate After Phase 3 Disappoints

AstraZeneca has called off the Interlink-1 Phase 3 head and neck cancer study of monalizumab, a potentially first-in-class NKG2A asset with Innate Pharma, after the investigational drug did not meet the set efficacy threshold in a futility interim analysis. There were no new safety findings, and AstraZeneca will share the data later, the company said. 

The news is a blow to Innate, which partnered with AstraZeneca over monalizumab in a $1.275 billion deal in October 2018. However, there is still hope for the drug in other ongoing studies, such as the Phase 3 Pacific-9 study in non-small cell lung cancer (NSCLC) and the Phase 2 NeoCOAST-2 study in the neoadjuvant early-stage lung cancer setting.

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Potential First-In-Class NKG2A Inhibitor

Sponsored by AstraZeneca, the Interlink-1 study evaluated monalizumab in combination with cetuximab vs cetuximab in patients with metastatic squamous cell carcinoma of the head and neck (R//M SCCHN) who have previously undergone platinum-based chemotherapy and PD-(L)1 inhibitors. The trial’s primary endpoint was overall survival in HPV-unrelated participants, with secondary endpoints including progression-free survival, overall response rate, and duration of response. 

Hopes were high for monalizumab after it showed promise in a Phase 1b/2 study of head and neck cancer, but following the Phase 3 results the drug apparently failed to deliver.

Monalizumab could make a comeback if it succeeds in the Pacific-9 lung cancer study, which will combine the drug with durvalumab (PD-L1) or AstraZeneca’s oleclumab (anti-CD73), or the Phase 2 NeoCOAST-2 study which will review the drug as a neoadjuvant for early NSCLC.

If approved, monalizumab could be the first NKG2A inhibitor to reach the market. Expressed in some immune cells such as natural killer (NK) and cytotoxic T-cells, NKG2A is part of an immune checkpoint. It is a receptor for HLA-E, which upon binding will inhibit and prevent the immune cell from killing the cell. Cancer cells may express HLA-E to escape destruction. Monalizumab, by inhibiting NKG2A, could reestablish the anti tumor response mounted by NK and T-cells, and may even show synergy with other cytotoxic antibodies.

Including the $50 million payment triggered by dosing the first patient in the Pacific-9 study, Innate has received $450 million to date. If commercialized, the company may reap low double-digit to mid-teen royalties on global sales excluding Europe, where Innate will receive 50% of the profits and losses. Innate is also responsible for 30% of Phase 3 development of monalizumab.

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Joy Lin

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