Expanded Access Program for recombinant BCG launches at first US site

U.S. Urology Partners has become the first site to offer recombinant BCG (rBCG) through an Expanded Access Program (EAP; NCT06800963) for patients with non–muscle invasive bladder cancer (NMIBC) who are eligible to receive intravesical TICE BCG, ImmunityBio announced in a news release.¹

The rBCG vaccine has been evaluated in phase 1/2 clinical trials in Europe.

The FDA authorized the EAP last month² to provide an alternative source of BCG to patients across the US in an effort to address the ongoing BCG shortage.

“Constrained BCG supply has improved stewardship of a limited resource but has come at a high cost to our patients,” explained Chad A. Reichard, MD, co-director of clinical research at Urology of Indiana, an affiliate of U.S. Urology, in the news release.¹ “rBCG represents a long overdue potential alternative but does not abrogate responsibility to ongoing diligence and discipline in BCG delivery.”

According to ImmunityBio, 60 sites are also in the process of launching the EAP.

To be eligible for the EAP, patients must have histologic confirmation of BCG-naïve NMIBC CIS or stage Ta and/or T1 papillary tumors, an absence of resectable disease after TURBT, and an ECOG performance score of 0, 1, or 2.³ Those enrolled in the program will receive an induction course of 19.2e8 colony-forming units of rBCG via intravesical administration. Safety measures will be assessed throughout the program.

“The shortage of BCG has real consequences, especially in many rural communities across the country where supply shortages have impacted the treatment of patients with bladder cancer,” said Christopher M. Pieczonka, MD, CEO and director of clinical research at Associated Medical Professionals, an affiliate of U.S. Urology Partners, in the release.¹ “I’m pleased U.S. Urology is at the forefront of offering rBCG and would like to thank ImmunityBio for their initiative to seek and secure authorization from the FDA for expanded access to this vital BCG alternative.”

According to ImmunityBio, the hope is that this program will help to address the ongoing shortage of TICE BCG in the US. The shortage, which ramped up in 2019, has posed challenges for the treatment of patients with NMIBC, for which BCG has been the standard of care since 1977. In the release, ImmunityBio cited a recent survey of 100 urologists, of which 57% reported they were unable to treat patients in the previous 12 months due to a lack of access to TICE BCG.

There is currently only 1 manufacturer of TICE BCG in the US. For the EAP, ImmunityBio has partnered with the Serum Institute of India, which develops rBCG, to provide an alternative source across the country.

“This is an incredibly exciting opportunity to expand the BCG supply to allow more patients to receive the full course of their cancer treatment, saving bladders and extending lives,” said Eugene B. Cone, MD, co-director of clinical Research at Urology of Indiana, an affiliate of U.S. Urology.

Data on rBCG

The rBCG vaccine (VPM1002BC) has been evaluated in phase 1/2 clinical trials in Europe as an immunotherapy in patients with NMIBC.^4,5 According to ImmunityBio, rBCG has 2 gene modifications that enable improved immunogenicity and safety vs other formulations of BCG. In clinical trials, the rBCG vaccine has already shown favorable safety and tolerability as well as enhanced immunogenicity in driving CD8+ and CD4 T cells compared with earlier strains of BCG, the company reported.

Specifically, the phase 1/2 trial of the therapy, conducted in patients with NMIBC who had failed conventional BCG, showed that 49.3% (95% CI, 32.1-64.4%) of patients treated with VPM1002BC remained recurrence-free at 1 year following treatment.⁵ At 2- and 3-year follow-up, the recurrence-free rates were 47.4% (95% CI, 30.4-62.6%) and 43.7% (95% CI 26.9-59.4%), respectively.

The therapy was also found to be safe and generally well tolerated. Grade 1, 2, and 3 treatment-related adverse events (AEs) occurred in 14.3%, 54.8%, and 4.8% of patients, respectively. No grade 4 or higher AEs were reported. In total, 2 of 42 patients were not able to complete 5 or more instillations during the induction period.

REFERENCES

1. ImmunityBio announces first dosing of recombinant BCG (rBCG) in the U.S. and 60 sites are in the process of launching. News release. ImmunityBio. Published online and accessed March 13, 2025. https://immunitybio.com/immunitybio-announces-first-dosing-of-recombinant-bcg-rbcg-in-the-u-s-and-60-sites-in-the-process-of-launching/

2. FDA authorizes ImmunityBio to provide recombinant BCG (rBCG) to urologists to address TICE BCG shortage. News release. ImmunityBio. February 19, 2025. Accessed March 13, 2025. https://ir.immunitybio.com/news-releases/news-release-details/fda-authorizes-immunitybio-provide-recombinant-bcg-rbcg

3. ResQ133A-NMIBC: Intravesical Recombinant Mycobacterium (rMBCG) in participants with NMIBC eligible to receive intravesical TICE BCG. ClinicalTrials.gov. Last updated January 31, 2025. Accessed March 13, 2025. https://clinicaltrials.gov/study/NCT06800963

4. Rentsch CA, Bosshard P, Mayor G, et al. Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy. Oncoimmunology. 2020;9(1):1748981. doi:10.1080/2162402X.2020.1748981

5. Rentsch CA, Thalmann GN, Lucca I, et al. A phase 1/2 single-arm clinical trial of recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC immunotherapy in non-muscle-invasive bladder cancer recurrence after conventional BCG therapy: SAKK 06/14. Eur Urol Oncol. 2022;5(2):195-202. doi:10.1016/j.euo.2021.12.006