Innate Pharma’s new checkpoint inhibitor, monalizumab, currently in development for solid tumours, is now being discontinued in head and neck squamous cell carcinoma (HNSCC). Monalizumab failed to meet a pre-defined threshold of efficacy during a planned futility interim analysis of the INTERLINK-1 Phase III study, which has led AstraZeneca, the drug’s co-developer, to terminate the study.
Monalizumab is an anti-NKG2A monoclonal antibody that aims to promote cancer cell killing mediated by NKG2A-expressing immune cells. NKG2A is considered to be a novel checkpoint in solid tumours. Monalizumab’s pivotal clinical trial in HNSCC, INTERLINK-1, was in combination with Eli Lilly’s EGFR antibody, Erbitux (cetuximab). The combination had previously demonstrated a 32.5 overall response rate in a Phase I/II study, with a very unclear benefit over Erbitux alone. As such, the Phase III failure was not a complete surprise to investors.
In non-small cell lung cancer (NSCLC), AstraZeneca and Innate are following a slightly different strategy with the pivotal PACIFIC-9 trial by targeting a population where AstraZeneca’s Imfinzi (durvalumab) is the current market leader. This population consists of Stage III unresectable patients following concurrent chemoradiation; monalizumab is being investigated in combination with Imfinzi, or with the novel anti-CD70 antibody oleclumab, versus Imfinzi as a single agent. Previous Phase II data from the COAST trial showed that both oleclumab and monalizumab can prolong progression-free survival (PFS) compared to Imfinzi alone. Specifically, the 12-month PFS for Imfinzi monotherapy was 33.9%, while for the combination with oleclumab, it was 62.6%, and for the combination with monalizumab, it was 72.7%. If these results hold up in the PACIFIC-9 study, a monalizumab combination could see very high clinical uptake in the Stage III unresectable setting.
While Innate and AstraZeneca are making an admirable effort to investigate novel checkpoint inhibitors, this is a high-risk, high-reward approach, especially considering the numerous recent failures of novel checkpoint molecules. Despite this, the failure of monalizumab in HNSCC is viewed as a temporary setback. According to previous GlobalData estimates, Imfinzi could become a blockbuster in the NSCLC unresectable setting, meaning that both oleclumab and monalizumab have a good chance of generating very lucrative combined revenue. Monalizumab is also being investigated in a Phase II study in the neoadjuvant and adjuvant NSCLC settings, which can be highly lucrative. PD-1 and PD-L1 inhibitors have, however, already started to infiltrate this area, making monalizumab a late-mover in this setting. Consensus analyst forecasts predict revenues for monalizumab to surpass $200m worldwide by 2028.
See Also:
How well do you really know your competitors?
Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.
Thank you!
Your download email will arrive shortly
Not ready to buy yet? Download a free sample
We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form
By GlobalData
Related Company Profiles
AstraZeneca Plc
Eli Lilly and Co
Innate Pharma SA