FDA Grants Breakthrough Therapy Designation to Debio 1143 In Front-Line Head and Neck Cancer

The FDA has granted Breakthrough Therapy Designation for Debio 1143, an inhibitor of apoptosis proteins, for the treatment of patients with a confirmed diagnosis of previously untreated, unresectable locally advanced squamous cell carcinoma of the head and neck in combination with cisplatin-based concomitant standard fractionation chemoradiation (CRT), the current standard of care (SOC), announced Debiopharm in a press release.¹

“This FDA assessment is a strong encouragement to expand investigations into other cancer types where the radio-sensitization effect of Debio 1143 could also provide further benefits over the current standard of care,” Sergio Szyldergemajn, MD, medical director of Oncology at Debiopharm, said in a statement.

The Breakthrough Therapy Designation is based on positive data from a phase II study which were presented at the European Society of Medical Oncology (ESMO) 2019 Congress. The analysis showed that the study met its primary end point and produced clinically compelling and statically significant data for the 4 secondary end points.²

In 96 patients, treatment with Debio 1143 plus cisplatin and radiotherapy (CRT) improved locoregional control (LRC) at 18 months by 21% compared cisplatin plus radiotherapy only (odds ratio, 2.69; 95% CI, 1.13-6.42;P=.026). Following 6 months of CRT, patients in the Debio 1143 had an overall response rate (ORR) of 67% versus the 48% observed in the placebo group. The complete response (CR) rates in these groups were 52% versus 38%, respectively. The median progression-free survival was 16.9 months in the placebo group and had not yet been reached in the Debio 1143 group (HR, 0.37; 95% CI, 0.18-0.76; P= .007). The median OS was not reached in either arm (HR, 0.65; 95% CI, 0.32-1.33; P= .243).³

Both arms showed comparable grade 3/4 adverse events (AEs) and severe AEs. The occurrence of grade 3 mucositis, dysphagia, and anemia were exceptions that occurred more commonly in patients who received Debio 1143 versus placebo. Additionally, 2 grade-5 AEs were reported in the placebo group.

The double-blind, randomized controlled study was conducted in 19 sites in France and Switzerland. The goal of the study was to compare the efficacy and safety of Debio 1143 and the SOC. Patients received either Debio 1143 at 200 mg/day for the first 14 days of 3-week cycles in combination with cisplatin in a 1-hour intravenous infusion on days 2, 23, and 44 given 0.5 hours after Debio 1143 plus radiotherapy given daily for 5 days per week over a 7-week period or matching placebo with SOC.

The primary end point of the study was the LRC rate at 18 months. The key secondary end points included PFS, ORR, CR rate, and safety.

A total of 95 patients were treated in the study. The median patient age was 58 years. Most patients were men (81%) with an ECOG performance status of 0 (56%), stage IV disease (84%), and oropharynx primary (67%). The background information of patients in the study revealed that 88% had human papilloma virus 16, 59% were alcohol consumers, and there was a median smoking history of 40-pack years across arms.

Debio 1143 is said to sensitize tumor cells to radio-chemotherapy by promoting programmed cell death and enhanced anti-tumor immunity. The study of Debio 1143 versus SOC is ongoing but no longer recruiting. The estimated study completion date is April 2020.

References

1. FDA Grants Breakthrough Therapy Designation for Debiopharm's novel chemo-radio sensitizer debio 1143 for front-line treatment of head & neck cancer [news release]. Lausanne, Switzerland: Debiopharm; February 27, 2020. https://prn.to/2PxQJQu. Accessed February 27, 2020.
2. Debiopharm's novel iap antagonist debio 1143 achieves outstanding phase ii results for high-risk head and neck cancer patients [news release]. Lausanne, Switzerland: Debiopharm; September 30, 2019. Accessed February 27, 2020.
3. Bourhis J, Sun X, Pointreau Y, et al. Double-blind randomized phase II results comparing concurrent high-dose cisplatin chemorradiation (CRT) plus debio 1143 or placebo in high-risk patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN): A GORTEC study.Annals of Oncol.2019; (suppl. abstract LBA65).