ASCO GU recap: Sam Chang, MD, on KEYNOTE-B15, SWOG S1602

In the following video, Sam S. Chang, MD, MBA, highlights 2 studies presented at the 2026 ASCO Genitourinary Cancers Symposium in San Francisco, California, that he believes are particularly impactful for clinicians treating bladder cancer. Chang highlighted data in both non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), emphasizing findings that may directly influence clinical decision-making.

Chang is chief of urologic oncology at Vanderbilt University Medical Center and the chief surgical officer at Vanderbilt Ingram Cancer Center in Nashville Tennessee.

One notable presentation was the phase 3 SWOG S1602 trial (NCT03091660), which evaluated alternative strains of BCG in BCG-naïve high-grade NMIBC.¹ The study compared the standard TICE strain of BCG with the Tokyo strain, which is not yet commercially available in the United States, and also evaluated whether subcutaneous priming with the Tokyo strain could enhance response to intravesical therapy. Participants were randomly assigned 1:1:1 to receive the TICE strain of BCG (n = 330), the Tokyo strain of BCG (n = 327), or intradermal priming with the Tokyo strain plus the intravesical Tokyo strain (n = 327). The primary end point was high-grade recurrence-free survival (HG-RFS).

The results demonstrated that the Tokyo strain was noninferior to the TICE strain regarding HG-RFS (HR, 0.82; 95.8% CI, 0.63 to 1.08). The estimated 5-year HG-RFS was 64% in the Tokyo arm vs 58% in the TICE arm. The study also demonstrated that subcutaneous priming with Tokyo strain BCG did not improve outcomes compared with intravesical BCG alone.

The study also evaluated safety and tolerability among the treatment strategies. Chang noted that adverse event profiles were broadly similar across the arms, although the Tokyo strain may have been associated with slightly fewer lower urinary tract symptoms (TICE, 3.7 points higher on 6-month Bladder Cancer Index urinary domain scores; 95% CI, 1.75 to 5.62; P < .001). Overall, the findings suggest that the Tokyo strain could serve as a viable alternative to the TICE strain—an important consideration given ongoing supply challenges with BCG in the US.

Chang also highlighted the phase 3 EV-304/KEYNOTE-B15 trial (NCT04700124), which evaluated perioperative treatment with enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in patients with platinum-eligible MIBC.² In this study, patients were randomanly assigned 1:1 to receive 4 cycles of the combination regimen (n = 405) or standard platinum-based chemotherapy (n = 403) prior to radical cystectomy, followed by the combination or observation, respectively. Over 80% of patients in both arms ultimately underwent surgery.

The trial generated significant interest during the meeting due to its strong efficacy signals, including a pathologic complete response rate of 55.8% with enfortumab vedotin plus pembrolizumab compared with a rate of 32.5% with chemotherapy (estimated difference, 23.4%; 95% CI, 16.7 to 29.8; 1-sided P < .0001). In addition to improved pathologic responses, the combination regimen demonstrated meaningful survival benefits. Two-year event-free survival was 79.4% with enfortumab vedotin plus pembrolizumab vs 66.2% with chemotherapy (HR, 0.53; 95% CI, 0.41 to 0.70; 1-sided P < .0001), while overall survival was 86.9% vs 81.3%, respectively (HR, 0.65; 95% CI, 0.48 to 0.89; 1-sided P = .0029).

Patients in the experimental arm also received additional adjuvant therapy with the combination following surgery, which Chang noted is an important consideration when interpreting the results. The findings prompted discussion among experts about whether the regimen could soon become a new standard perioperative approach for patients with MIBC, while also raising future questions about treatment de-escalation and whether bladder-preserving strategies or reduced systemic therapy may eventually be possible for select patients.

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://www.asco.org/abstracts-presentations/257313

2. Galsky MD, Pérez-Valderrama B, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA630. https://www.asco.org/abstracts-presentations/256834/abstract