The US FDA has granted a Breakthrough Therapy Designation for Debio 1143, an IAP antagonist, for the treatment of patients with a confirmed diagnosis of previously untreated, unresectable locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
The indication is granted in combination with the current standard of care, cisplatin-based concomitant standard fractionation chemoradiation therapy (CRT).
Ongoing clinical investigations have been developed to evaluate the benefit of increasing tumour cell sensitivity to CRT, making the addition of Debio 1143 a highly promising strategy for radio-oncologists to improve treatment outcomes for high-risk LA-SCCHN.
This Breakthrough Therapy Designation is based on the clinically compelling phase II study results presented at the ESMO Congress 2019 in Barcelona, Spain.
They revealed a very significant improvement of the primary endpoint locoregional control rate at 18 months after CRT (21% improvement vs. control arm) and a marked Progression-Free Survival (PFS) benefit vs. the CRT+placebo arm after a 2-year follow-up period (HR=0.37, p=0.007). In addition, the compound showed a predictable and manageable safety profile, that did not compromise the full delivery of standard CRT.
“Despite today’s current standard of care, high-risk locally-advanced head and neck cancer remains an area of unmet medical need,” said Angela Zubel, chief development officer, Debiopharm, in a press release by Debiopharm.
Breakthrough Therapy Designation is intended to expedite the clinical development and review of medicines showing substantial improvements in serious or life-threatening conditions so that patients can access innovative therapies as soon as possible.
Squamous cell carcinoma of the head and neck (SCCHN) is the 6th most common cancer type worldwide, with more than half of patients diagnosed with locally-advanced (LA) disease. High-risk LA-SCCHN patients, including HPV negative oropharyngeal cancer (OPC) patients and heavy smokers, face a poor prognosis even with the current standard of care (SOC) as more than half of them will relapse.
The consequences of LA-SCCHN have a heavy impact on the quality of life and social interactions, affecting how patients look, talk, eat and breathe. Additional therapies are needed to ensure better outcomes for patients facing this devastating condition.
Debio 1143 is a potential first-in-class oral antagonist of IAPs (inhibitor of apoptosis proteins), that sensitizes tumour cells to radio-chemo therapy by promoting programmed cell death and fostering anti-tumor immunity.
The clinical benefit observed in LA-SCCHN patients suggests that the integration of Debio 1143 into widely used CRT regimens is a promising investigational approach over a broad range of cancer types.
Currently poised to enter into a phase III pivotal trial later this year in combination with CRT in head & neck cancer, the compound is also being investigated along with immune checkpoint inhibitors (PD-1/PD-L1) in various solid tumours.
Over 200 patients have been treated so far with Debio 1143 in various indications and lines of treatment, showing an adequate and consistent safety profile across studies, the Swiss firm said.