LBA02-04 NOVEL WEEKLY IMMUNOTHERAPY DOSING WITH AVELUMAB TOLERATED DURING BACILLUS CALMETTE-GUERIN INDUCTION THERAPY: INITIAL RESULTS OF THE ABC TRIAL

Abstract

INTRODUCTION AND OBJECTIVE: The optimal management of Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) remains unclear. Given the limited treatment options, the FDA suggested single arm studies may provide evidence of treatment efficacy. Immunotherapy responses in patients with metastatic urothelial carcinoma has created interest in combination therapy with BCG for patients with BCG-unresponsive NMIBC. The optimal dosing of immunotherapy in combination with BCG treatment is not clear. This study evaluates the safety and tolerability of a novel intense weekly dosing regimen of avelumab during BCG induction for patients with BCG-unresponsive NMIBC. METHODS: NCT03892642 is an open label Phase Ib trial of adults with a history of NMIBC and prior BCG therapy. Following tumor resection, patients underwent a 6-week BCG induction with weekly avelumab infusion (10 mg/kg IV) followed by BCG maintenance therapy with weekly avelumab for 12 months. Between BCG treatments bi-weekly avelumab infusion (10 mg/kg IV) was given. The primary endpoint was completion of a full induction course, five out of six treatments with BCG and avelumab, within eight weeks of treatment initiation. The secondary endpoint is completion of 6 months of maintenance treatment. RESULTS: Out of 18 patients, 4 were Female and 14 Male. There were 2 Black, 16 White, and no Hispanic or Latino patients. Median age was 69.9 ±9.3 years (range, 53-84). The majority of patients (9) had T1 stage tumors, 5 patients had Ta, and 4 patients had Tis. A total of 15/18 (83%) patients were able to complete induction therapy with 16 receiving at least 5 BCG treatments and 15 receiving at least 5 avelumab treatments. This exceeded the 60% anticipated completion rate. At the three-month cystoscopy, 13/15 (87%) patients remained on treatment, 10 without evidence of cancer and 3 with persistent disease (2 CIS, 1 Ta). No drug-attributable grade 4 or 5 AE's were observed. All patients who discontinued treatment were included in the safety analysis. During induction therapy 2 (11%) patients had probable drug related grade 3 adverse events which were: infusion related reaction (avelumab), and sepsis (BCG). Followup remains ongoing. CONCLUSIONS: In BCG-unresponsive NMIBC patients, induction therapy with combined BCG and avelumab was safe and well tolerated. This study supports continued efforts to evaluate the optimal dosing regimen to synergize BCG and immunotherapy.