Debio 1143, a potential first-in-class inhibitor of apoptosis proteins, demonstrated a statistically and clinically significant overall survival improvement when used in combination with chemoradiotherapy as treatment of patients with high-risk locally advanced squamous cell carcinoma of the head and neck, according to a press release from Debiopharm.
Debio 1143, a potential first-in-class inhibitor of apoptosis proteins (IAP), demonstrated a statistically and clinically significant overall survival (OS) improvement when used in combination with chemoradiotherapy (CRT) as treatment of patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), according to a press release from Debiopharm.1
In the phase 2 study, 96 patients were randomized to Debio 1143 plus CRT versus CRT monotherapy. The OS P value was .0261 at 3-year follow-up, showing the potential to half the risk of mortality for patients receiving the combination compared with CRT alone.
"These 3-year follow-up results could have major implications for [patients with] high-risk head and neck cancer, especially those with negative HPV status who appear to be associated with the poorest prognosis. As the compound is now advancing into phase 3 [trial], we will be able to gather further evidence for this CRT enhancing IAP antagonist that has the potential to become a standard-of-care treatment for radiation oncology," Jean Bourhis, MD, department head of Radio-Oncology at the University Hospital of Lausanne and lead investigator of the study, said in a statement.
Debio 1143 also showed sustainability in the results of another phase 2 trial (NCT02022098).2 In this study, improvements in progression-free survival (PFS) rates and duration of response that were statistically significant. The median PFS had not been reached for those receiving Debio 1143 and was 16.9 months in the placebo group (HR, 0.37; 95% CI, 0.18-0.76; P =.0069). There was a 32% difference in PFS at 2 years as well (72% vs. 41%, respectively; P =.0026).
The safety profile for this agent in combination with CRT remained predictable and manageable from 2 years of follow-up to 3 years of follow-up. This treatment was given in 3-week cycles starting at study initation.1
Earlier this year, Debio 1143 was granted a Breakthrough Therapy Designation from the FDA for the treatment patients with a confirmed diagnosis of previously untreated, unresectable LA-SCCHN in combination with cisplatin-based concomitant standard fractionation chemoradiation. This regimen will be used in a phase 3 pivotal trial in September. If approved as treatment in this setting, it will be the first new option for patients with head and neck cancer in the past 25 years.
"This is an important step forward for [patients with] head and neck cancer and the research community as this potential front-line therapy could change the way these patients are treated from the start," Angela Zubel, chief development officer of Debiopharm, said in a press release. "I am very encouraged by improvement of long-term outcomes observed in our study. These results indicate that Debio 1143 in combination with CRT has the potential to prolong patient lives and achieve better control over their disease."
1. Debiopharm's IAP Antagonist Significantly Improves Overall Survival of High-Risk Head & Neck Cancer Patients. News Release. Debiopharm. August 13, 2020. Accessed August 13, 2020. https://prn.to/2PPHXNl
2. S X-S, Tao Y, Le Tourneau C, et al. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Lancet Oncol. Published online August 3, 2020. doi:10.1016/S1470-2045(20)30327-2