SWOG S1602: Tokyo BCG is noninferior to TICE in NMIBC

Findings from the phase 3 SWOG S1602 trial (NCT03091660) found the BCG Tokyo strain was noninferior to TICE for high-grade non–muscle invasive bladder cancer, suggesting a potential strategy to ease ongoing BCG shortages, although intradermal priming showed no added benefit.¹

Robert Svatek, MD, MSCI, a professor of medicine in the Division of Urologic Oncology in the Department of Urology at The University of Texas Health Science Center at San Antonio, began his presentation at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium with a brief history of BCG’s development.

“This story begins in the early 1900s, with the emergence of the first BCG strain, [which] was created after 13 years of serial passage at the Pasteur Institute. While they waited for loss of virulence, and once they identified a strain that was safe, they then disseminated it globally. Then, these ‘daughter strains’ evolved in laboratories all over the world, and they continued to evolve until the 1960s, when they instituted archival seed lots. Using comparative genomics, we now know that there are a lot of differences between these strains.”²

Svatek then displayed a genealogy tree.

“We can see that early strains, such as BCG Tokyo, differ significantly from so-called late strains, like BCG TICE, based on genetic deletions, insertions, and single-nucleotide polymorphisms. We also know that these genetic changes contribute to differences in immune reactivity in the laboratory and in patients. Now, whether or not those differences influence the efficacy of BCG in treating bladder cancer is unclear.²

“Why does this matter?” Svatek continued. “It matters because in the United States, there is only 1 strain that is FDA approved and used, and that is BCG TICE. We all know that shortages in BCG continue to happen, and they have substantial on the patient’s outcome. In fact, there’s a shortage right now.”

Along with comparing BCG strains, Svatek explained that another goal of SWOG 1602 was to evaluate a novel approach to improving systemic immunity to BCG. The study population consisted of patients with carcinoma in situ (CIS), high-grade TA, or high-grade T1 bladder cancer. Stratification was done according to stage (CIS only vs Ta vs T1 vs CIS plus papillary) and age (75 or younger and older than 75 years). Patients were randomly assigned 1:1:1 to receive intravesical BCG TICE (50 mg/dose), intravesical BCG Tokyo strain (80 mg/dose), or priming with intradermal BCG (Tokyo 100 μL at 0.5 mg/mL plus intravesical BCG (Tokyo 80 mg/dose). The primary end point was high-grade recurrence-free survival.

Svatek outlined the co-aims of the trial:

• to evaluate noninferiority of BCG Tokyo vs TICE

• to evaluate the superiority of priming.

Patients received BCG in an induction phase (6 weekly) followed by maintenance (3 weekly) at 3, 6, 12, 18, 24, 30, and 36 months. For those who underwent priming, intradermal BCG was administered 21 days prior to intravesical BCG. All patients were followed for 5 years.

Regarding baseline characteristics, “The demographic are what you would expect from this population,” Svatek said. There were 330, 327, and 327 patients in the TICE, Tokyo, and Prime cohorts, respectively. In each cohort, more than 80% of patients were male.

Svatek reported high rates of completion of the induction phase across the cohorts: 325 (95%), 319 (98%), and 315 (96%) patients in the TICE, Tokyo, and Prime cohorts completed induction treatment, respectively. A total of 116 (34%), 148 (45%), and 161 (49%) patients in the TICE, Tokyo, and Prime cohorts completed 1 year or less of maintenance treatment, respectively. A total of 159 (48%), 126 (39%), and 118 (36%) patients in the TICE, Tokyo, and Prime cohorts completed more than 1 year of maintenance treatment. Eighteen (5%), 39 (12%), and 29 (9%) patients in the TICE, Tokyo, and Prime cohorts were lost to follow-up or withdrew prior to 1° outcome.

Turning to the first co-aim, Svatek said that the Tokyo strain was found to be noninferior to TICE (HR: 0.82, 95% CI, 0.63-1.08). The Tokyo strain was also noninferior to TICE in treating CIS. Biopsy-proven complete response (CR) at 6 months (+/- 21 days) was seen in 80 (70.2%) patients receiving TICE vs 73 (66.4%) in patients receiving Tokyo strain. The 2-year CR duration was 84% in patients receiving TICE vs 87% in patients receiving the Tokyo strain.

Regarding safety, Svatek reported a 1.2% incidence of grade 4 toxicity in patients receiving TICE vs 0% in patients receiving the Tokyo strain. There was an 11% incidence of grade 3 toxicities in patients receiving the Tokyo strain compared with 5% in patients receiving TICE. No grade 5 toxicities were observed in the study. The most common adverse events in patients receiving either strain included hematuria, renal urinary, and urinary tract pain.

Looking at patient-reported outcomes, the investigators utilized the Bladder Cancer Index and looked at urinary domain scores at 6 months. TICE was found to be 3.7 points (95% CI, 1.75-5.62; P < .001) higher (indicating better urinary quality of life) at 6 months.

“However, commonly estimated thresholds for minimally important difference are typically in the range of 5 to 10, so at 3.7 we conclude that this is of limited clinical relevance,” Svatek said.

Regarding the second co-aim, “Unfortunately, priming did not improve the outcomes for patients,” Svatek said (HR: 1.0; 95% CI, 0.76-1.33). In patients with CIS, priming did not result in an increase in CR.

“In conclusion, Tokyo BCG is noninferior to TICE. This means that the BCG shortage could be mitigated with the Tokyo strain. Compared to TICE, Tokyo had slightly higher bother and grade 3 adverse events. Priming did not improve outcome,” Svatek said.

REFERENCES

1. Svatek RS, Tangen C, Meeks JJ, et al. SWOG 1602: A phase III randomized trial to evaluate BCG strain differences and priming with intradermal BCG before intravesical therapy for BCG-naïve high-grade non-muscle invasive bladder cancer (NCT #03091660). Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA629. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16917?presentation=257313

2. Brosch R, Gordon SV, Garnier T, et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A. 2007;104(13):5596-5601. doi:10.1073/pnas.0700869104