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.

Related article: Bristol Myers Squibb Provides an Update on Kidney Cancer Treatment

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.

Related posts:

First AI-Designed Drug to Enter Phase I Clinical Trial AstraZeneca’s Imfinzi Beats Standard of Care in Advanced Biliary Tract Cancer Merck Breaks Off Keytruda Combo Trial with AstraZeneca, Begins Another with Imugene AstraZeneca’s Liver Cancer Treatment Combination Snatches FDA Approval

Author

Joy Lin

Without knowledge, there is no imagination. Without imagination, knowledge is meaningless