Breakthrough.

Top Line: In a breakthrough move to incorporate radiation into the pharm development rat race, the FDA has granted a “breakthrough therapy” status to the systemic agent Debio 1143.

The Study: Debi who? Get ready for a double-negative. Debio 1143 is technically an antagonist of inhibitor of apoptosis proteins (IAPs). In other words, it ramps up apoptosis to serve as an effective chemo-radio-sensitizer by not only killing more cancer but doing so in an organized fashion that promotes anti-tumor immunity. The novel indication (concurrent to radiation in the upfront setting) for this breakthrough approval is based on impressive results from a phase 2 trial reported at ESMO 2019. In it, 96 patients receiving standard upfront radiation concurrent with cisplatin for locally-advanced head and neck cancers (88% HPV+)  received either Debio 1143 or placebo orally for the first 14 days of each 3-week cycle of cisplatin. At 18 months, the primary endpoint of locoregional control was significantly improved with the addition of Debio 1143 (OR 2.6). And while it’s still too early to tell, median progression-free and even overall survival times are trending in the same direction.

TBL: In a landmark decision, the FDA has fast-tracked a novel drug specifically as a radio-sensitizer. | Bourhis, ESMO 2019