Aveluamab With BCG Induction Shows Early Safety/Tolerability in BCG-Unresponsive NMIBC

Data from the phase 1b ABC study show that the addition of avelumab to BCG induction therapy was safe and well tolerated in patients with BCG-unresponsive non-muscle invasive bladder cancer.

The use of combination induction therapy of avelumab (Bavencio) and Bacillus Calmette–Guérin may be safe and tolerable for patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), according to results from the phase 1b ABC study, presented during the American Urological Association 2021 Annual Meeting.1

“We know that BCG installation causes a systemic immune response as measured by increased urinary cytokines and serum cytokines that occurs around 4 weeks into induction therapy. We also know that immunotherapy has a time bearing clearance based on pharmacokinetics,” Kelly Stratton, MD, urologic oncologist, Stephenson Cancer Center, University of Oklahoma, explained during a virtual presentation at the meeting.

The aim of the study was to evaluate the optimization of immunotherapy in patients with NMIBC who may require novel dosing regimens linked to BCG administration.

In the trial, patients received induction BCG therapy, followed by maintenance BCG therapy for up to 12 months. At each BCG treatment, patients also received an avelumab infusion. When patients were not receiving BCG, they received avelumab infusions every 2 weeks.

The primary end point of the study was to complete a full induction course within 8 weeks of patients starting treatment, defined as at least 5 of 6 treatments of BCG plus avelumab. Secondary end points included tolerability, measured by the 6-month completion rate (completion of at least 2 of 3 maintenance treatments within a 5-week period at 6 months); 3- and 6-month CR rates; recurrence-free survival; cystectomy-free survival; and overall survival.

Key inclusion criteria consisted of histologically or cytologically documented NMIBC; BCG unresponsive; ECOG performance score of 0 to 2; aged 18 years or older; life expectancy of weeks or more; adequate hematologic and end-organ function; evidence of locally advanced or metastatic bladder cancer; evidence of extravesical bladder cancer; active central nervous system metastases; prior treatment with a PD-L1 inhibitor; and prior radiation to the bladder.

Median age was 70 years (range, 53-84). The majority of patients were male (78%), White (89%), and had T1 stage disease (n = 9).

“This was a heavily pretreated group, with 8 patients receiving multiple BCG induction treatments, and 4 patients previously enrolled on the SWOG 1602 trial,” Stratton said.

In total, 15 of 18 patients (83%) completed induction therapy, 16 patients received at least 5 BCG treatments, and 15 patients received at least 5 avelumab treatments, which exceeded the 60% anticipated completion rate, Stratton said.

At the 3-month cystoscopy, 13 of 15 patients (87%) remained on treatment, 10 of 15 (67%) experienced a complete response (CR), and 3 of 15 had persistent disease.

In addition, 5 patients (28%) have completed 12 months of treatment—all with CRs, and 2 patients remain on treatment.

Serious adverse events (AEs) occurred in 3 patients (17%), including 2 grade 3 AEs during induction (infusion reaction and sepsis) and 1 grade 3 AE during maintenance therapy (myasthenia gravis). No treatment-related grade 4/5 AEs were seen.

“This study evaluated induction therapy with combined BCG and avelumab, which appeared safe and well tolerated in BCG, unresponsive, non-muscle invasive bladder cancer patients,” Stratton said. “This study supports continued efforts to evaluate the optimal dosing regimen to synergize BCG and immunotherapy.”

Reference

Cookson M, Tripathi A, Patel S, et al. Novel Weekly Immunotherapy Dosing with Avelumab Tolerated During Bacillus Calmette-Guerin Induction Therapy: Initial Results of the ABC Trial. Presented at: 2021 American Urologic Association Annual Meeting; September 10-13, 2021; Virtual. Abstract LBA-02-04.