Combination Panvac-BCG does not significantly improve outcomes in non–muscle invasive bladder cancer

Clinical outcomes, including delay to recurrence, were not significantly improved for patients with bacillus Calmette-Guérin-unresponsive non–muscle invasive bladder cancer undergoing treatment with a combination of the recombinant pox-viral vector vaccine Panvac and bacillus Calmette-Guérin (BCG).¹

Results of the phase 2 study (NCT02015104) were presented at the 2021 American Urologic Association Annual Meeting.

Patients with high-grade NMIBC who did not respond to 1 or more induction courses of intravesical BCG were randomized to receive BCG (n = 15) or BCG plus Panvac (n = 15). The 12-month recurrence-free survival (RFS) rate was 42.9% (95% CI, 22.9%-80.0%) for those who received BCG alone compared with 44.4% (95% CI, 24.8%-79.9%) for those who received the combination (P = .971).

The median time to recurrence was 11.7 months vs 9.9 months, respectively (P = .77). The RFS rate for entire population was 43.3% (95% CI, 27.9%-66.8%).

The 12-month progression-free survival rates were 79.6% (95% CI, 56.9%-100%) and 78.6% (95% CI, 59.8%-100%) for patients treated with BCG alone and BCG plus Panvac, respectively.

Four patients from the BCG alone arm and 5 patients from the combination arm sought radical cystectomy following treatment.

In terms of baseline histologic characteristics, 14 patients had Ta, 7 had T1, 6 patients had carcinoma in situ alone, 2 had carcinoma in situ with Ta, and 1 had carcinoma in situ with T1. Additionally, 33% of patients (n = 10/30) had at least 2 prior induction courses of BCG.

The vaccine is designed to enhance the presentation of CEA and MUC-1, which are overexpressed in certain cancers, and activate cytotoxic T-lymphocyte response. The therapy consists of a recombinant vaccinia viral vector, a modified vaccinia Ankara-Bavarian Nordic, and a recombinant fowlpox vector. It is administered via a vaccinia priming dose, followed by multiple boosting doses of the fowlpox vector.²

Participants enrolled to the phase 2 trial received BCG in 6 weekly injections; those in the Panvac arm received the vaccine in 5 injections over 15 weeks.³

In the inclusion criteria for the study, investigators noted that all subclassifications for BCG failure would be considered for inclusion into the study, including BCG-refractory, -resistant, and -relapsing.

Investigators noted in the abstract that the trial was “unique” stating, “It originated prior to the definition of BCG-unresponsive disease and at least a third of the patients on this trial were already BCG unresponsive upon enrollment and received more BCG.”¹

In a guidance for developing drugs and biologics for treatment, the FDA defined BCG-unresponsive disease as having at least 1 of the following characteristics: persistent or recurrent carcinoma in situ with or without recurrent Ta/T1 disease within 12 months of the completion of adequate BCG therapy, recurrent high-grade Ta/T1 disease within 6 months of the completion of adequate BCG therapy, and/or T1 high-grade disease at the first evaluation after a BCG induction course.⁴

Further, the FDA defined adequate BCG is defined as at least 5 of 6 doses of an induction course plus at least 2 of 3 doses of maintenance therapy, or at least 5 of 6 doses of an induction course plus at least 2 of 6 doses of a second induction course.⁴

“Unlike [ongoing] trials, this trial had a comparison group of BCG alone and, despite the heavy pretreatment in up to a third of patients, the RFS in both arms was still comparable to what has been seen in current BCG unresponsive trials,” the investigators concluded.¹

The abstract was presented by Ragheed Saoud, MD, a urologist at Northwell Health in Riverside, New York.

References

1. Saoud R, Telfer S, Marfur M, et al. Clinical outcomes of a randomized, prospective, phase II study to determine the efficacy of bacillus Calmette-Guerin (BCG) given in combination with Panvac versus BCG given alone in adults with high grade BCG-refractory non-muscle invasive bladder cancer. J Urol. 2021;206(suppl3):e302. doi:10.1097/JU.0000000000002001.14

2. CEA-MUC-1-TRICOM vaccine CV301. National Cancer Institute. Accessed September 13, 2021. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/cea-muc-1-tricom-vaccine-cv301

3. Study of bacillus Calmette-Guerin (BCG) combined with Panvac versus BCG alone in adults with high grade non-muscle invasive bladder cancer who failed at least 1 course of BCG. ClinicalTrials.gov. Updated January 22, 2020. Accessed September 13, 2021. https://clinicaltrials.gov/ct2/show/NCT02015104

4. BCG-unresponsive nonmuscle invasive bladder cancer: developing drugs and biologics for treatment guidance for industry. FDA. 2018. Accessed September 13, 2021. https://www.fda.gov/media/101468/download