Xevinapant Phase II Study Displays Improved Efficacy Outcomes in Head and Neck Cancer

Head and neck cancer refers to a variety of tumors that appear in or near the throat, larynx, nose, and sinuses. The treatment for this condition is challenging, and many promising trials have failed to meet their targets.

Xevinapant is a first-in-class potent oral antagonist of IAPs (Inhibitor of Apoptosis Proteins) being investigated in the Phase III TrilynX trial in the patients with unresected LA SCCHN. This drug was also granted Breakthrough Therapy Designation by the US FDA in 2020.

In ESMO 2022 the company presented the five-year overall survival (OS) data, and reported that the primary endpoint of participants achieving locoregional control (LRC) at 18 months from the end of chemo-radiation therapy (CRT) was significantly improved with xevinapant vs placebo. The 3-year PFS rate of 72% was observed with xevinapant + CRT vs 36% PFS rate in placebo. The addition of xevinapant to CRT nearly doubled the cure rates. The drug + CRT displayed a 5-year OS rate of 53% vs 28% in the placebo arm and the risk of death was more than halved. In fact, the drug improved the OS across all the prespecified groups in the study. The duration of response (DoR) was also prolonged with the addition of xevinapant. As per the 3-year analysis, the DoR of xevinapant + CRT was 79 % vs 36% with the placebo arm. Thirty-one complete responses (CRs) and 6 partial responses (PRs) were observed with xevinapant vs 26 CRs and 9 PRs with placebo. The drug was successful in reducing the risk of death or disease progression after initial response was reduced by 79%. 

The safety profile was similar between arms and no patient in the xevinapant arm died due to TEAEs vs 2(4.3%) in the placebo arm.

The addition of xevinapant to the standard of care CRT, significantly improved the efficacy outcomes without increasing the toxicity and it is the first study in decades to improve the cure rate by adding a new treatment to SoC (cisplatin + RT). The positive Phase II results indicate the potential of xevinapant to restore cancer cell sensitivity to apoptosis and enhance the effects of chemotherapy and radiotherapy.

KOL insights

“There is a definite need for better therapeutic options for patients with unresected locally advanced HNC. The five-year results of this randomized Phase II study show improved effectiveness outcomes for these patients compared to standard of care, and these results indicate the possibility that xevinapant may lead to a significant increase in the percentage of patients who are cured after definitive therapy.”– Expert Opinion

Learn more about key developments: Head and neck cancer (HNSCC) Market Outlook