A phase 2 study found that data from a 3-year follow up showed statistically significant improvements in overall survival for patients with high-risk locally advanced squamous cell carcinoma of the head and neck treated with an IAP antagonists with chemo-radiation therapy.
Data from a 3-year follow up found that an inhibitor of apoptosis proteins (IAPs) antagonist with chemo-radiation therapy significantly improved overall survival (OS) for patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) compared to the control group, a Debiopharm press release announced.1
The data also confirmed the statistically significant improvements from the 2-year outcomes published in Lancet across other end points including the doubling of the progression free survival (PFS) rate along with superior duration of response.
"These 3-year follow-up results could have major implications for high risk head and neck cancer patients, especially those with negative HPV status who appear to be associated with the poorest prognosis,” lead investigator of the study, Jean Bourhis, said in a press release. “As the compound is now advancing into phase 3, we will be able to gather further evidence for this radio-chemo enhancing IAP antagonist that has the potential to become a standard-of-care treatment for radiation oncology."
The results found that locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39–69) of 48 patients in the Debio 1143 group versus 16 (33%; 95% CI, 20–48) of 48 patients in the placebo group (odds ratio [OR], 2.69; 95% CI, 1.13–6.42; P= .026).
More, grade 3 or worse adverse events (AEs) were seen in 41 of the 48 patients in the Debio 1143 group and in 41 of the 47 patients in the placebo group.2 Common grade 3 to 4 AEs in the Debio 1143 and placebo groups included dysphagia (50% vs 21%, respectively), mucositis (31% vs 21%), and anemia (35% vs 23%). No deaths were recorded due to adverse events from treatment.2
"This is an important step forward for head & neck cancer patients 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 for Debiopharm, said in a press release.
The randomized phase 2 study evaluated the efficacy and safety of the IAP antagonist and chemo-radiation therapy combination to treat patients with LA-SCCHN. The data included 96 patients with La-SCCHN, 48 of which were randomly assigned to the Debio 1143 group and 48 patients to the placebo group.
The data shows that the inhibition of IAPs is a novel and promising approach which warrants a phase 3 study expanding the therapeutic options for patients. The researchers also believe this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator.
The compound received breakthrough therapy designation from the FDA in February 2020.
“I am very encouraged by improvement of long-term outcomes observed in our study,” said Zubel. “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]. Lausanne, Switzerland. Published August 13, 2020. https://www.prnewswire.com/news-releases/debiopharms-iap-antagonist-significantly-improves-overall-survival-of-high-risk-head--neck-cancer-patients-301111646.html. Accessed August 13, 2020.
2. Sun X, 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. DOI:https://doi.org/10.1016/S1470-2045(20)30327-2.