Introduction:

Patients with bacillus Calmette-Guérin (BCG)-exposed non-muscle-invasive bladder cancer (NMIBC) comprise a large population with a critical need for more effective treatments. Current standard of care is re-treatment with BCG alone, but only ~50% of patients derive clinical benefit. Although intravesical gemcitabine/docetaxel is sometimes used, studies have found that GemDoce is no better than re-treatment with BCG alone for BCG-exposed NMIBC.

A chemoimmunotherapy strategy of intravesical gemcitabine with BCG (GemBCG) combines the two most effective, inexpensive, and commonly used NMIBC treatments. A phase I/II (n=52) trial was initiated of GemBCG in BCG-exposed NMIBC (NCT04179162). GemBCG has minimal side effects, an outstanding early efficacy signal (6-month complete response of 97% [28/29] in patients with CIS compared with expected ~50% with BCG alone for BCG-exposed CIS), and promising preliminary longer-term efficacy (18-month high-grade recurrence-free survival [HG-RFS] of 76% compared with ~45-55% with BCG alone, GemDoce, and recombinant BCG in BCG-exposed NMIBC). 

Methods:

We initiated the “GAIN” trial (A032303), a prospective, multicenter, open-label phase III study of patients with BCG-exposed NMIBC randomized to re-treatment with BCG only or GemBCG. The primary objective is to determine whether GemBCG improves HG-RFS compared with BCG alone. BCG-exposed NMIBC is defined as a high-grade NMIBC (Ta, T1, Tis/CIS) that has recurred within 24 months of prior BCG but does not meet BCG-unresponsive NMIBC criteria. 

Inclusion is liberal, allowing for more than one prior BCG induction course/prior maintenance BCG; any prior systemic or intravesical agents for NMIBC (including gemcitabine); non-invasive urothelial carcinoma of the prostatic urethra and treated UTUCC. Patients with current/prior MIBC and prior intolerance of any intravesical therapies are excluded. Other notable aspects: NCI’s new streamlined data initiative, pragmatic design to improve generalizability, and week-13 cystoscopic biopsies in all participants for earlier detection of BCG-unresponsive disease and objective “benchmarking” of urinary biomarkers. Support: U10CA180821, U10CA180882;https://acknowledgments.alliancefound.org.  

Results:

Conclusion:

Funding: U10CA180821, U10CA18088