97P - BEAR study: A single-arm, phase II trial of BI-754091 and afatinib for refractory esophageal squamous cell carcinoma

Background

EGFR inhibitors could increase MHC class-I presentation and sensitize tumor cells to CD8+ T cell–mediated killing, leading to a synergic efficacy in combination with PD-1 blockade. Afatinib also showed response as monotherapy in the treatment of refractory esophageal squamous cell carcinoma (ESCC). Herein, we report preliminary results of a phase II study of BI-754091 and afatinib in refractory ESCC patients.

Methods

Patients with refractory ESCC were eligible to receive afatinib 30 mg once daily and BI-754901 240 mg on day 1, in a 3-week cycle. With Optimal Simon’s two-stage design and (p0=0.17, p1=0.35) for objective response rate (ORR, proportion of patients with complete or partial response [CR/PR]) and given error probabilities (one-sided alpha=0.05; beta=0.2), 16 evaluable patients were needed in the first stage. If 4 or more patients with objective response, the study would be extended to the second stage. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. The PR should be confirmed by two consecutive image examinations.

Results

Between August 2021 and February 2022, a total of 19 patients were enrolled as the intention-to-treat (ITT) population. Three patients withdrew early after the first cycle of treatment. With a median follow-up of 7.4 months (95% confidence interval [CI], 5.2-7.9), 7 patients achieved confirmed PR and 7 patients (36.8%) got stable disease, with the ORR of 36.8% (95% CI, 16-62%) in ITT population. The median progression-free survival was 5.3 months (95% CI, 3.8-6.1) in 16 evaluable cases. The common all grades of adverse events were afatinib-related diarrhea (47.5%), mucositis (36.9%), acneiform rash (31.6%). One patient suffered from grade 2 pneumonitis. No treatment-related death was reported.

Conclusions

By the observation of 7 patients with confirmed PR in the first stage, the second stage would be started for final enrollment to 44 evaluable cases.

Clinical trial identification

NCT04839471.

Editorial acknowledgement

Legal entity responsible for the study

The authors without further recourse to the authors.

Funding

Boehringer Ingelheim.

Disclosure

All authors have declared no conflicts of interest.