ESMO 2025 – Potomac marches step for step with Crest
Imfinzi and sasanlimab look nearly identical, but it’s a different story for Roche’s Tecentriq.
Imfinzi and sasanlimab look nearly identical, but it’s a different story for Roche’s Tecentriq.
If Pfizer’s Crest trial of sasanlimab in non-muscle invasive bladder cancer set the bar for AstraZeneca’s very similarly designed Potomac study of Imfinzi, then the latter trial has met that bar with numbers that look uncannily similar.
The same can’t be said for Alban, a study of Roche’s Tecentriq in the same setting, whose results were unveiled alongside Potomac in late-breaking presentations at ESMO on Friday. In the race to market AstraZeneca is slightly ahead, having filed the Potomac data in the EU; no US filing has publicly been disclosed in this use either for Imfinzi or sasanlimab.
The precise setting in question is non-muscle invasive bladder cancer patients naive to BCG, a first-line standard of care. Potomac, Alban and Crest all primarily tested the addition of an anti-PD-(L)1 antibody on top of BCG induction and maintenance, versus BCG induction and maintenance alone. Astra had toplined Potomac as positive in May.
Nearly identical?
With a minor caveat, the Potomac data look nearly identical to the results Pfizer put up in April at the American Urological Association meeting, from the Crest trial of sasanlimab, its subcutaneously delivered anti-PD-1 molecule.
The key difference was their primary endpoints: event-free survival for Crest, and disease-free survival for Potomac. Both are measures of a cancer’s progression, but the former probably captures a slightly wider range of “events”, including the failure to undergo surgery, for instance.
This subtlety aside, in Potomac Imfinzi plus BCG yielded a 0.68 hazard ratio (p=0.015), with 82% of patients being disease-free at 36 months, versus 77% of those who got BCG alone. In Crest sasanlimab plus BCG yielded the same 0.68 hazard ratio, with an identical 82% of patients being event-free at 36 months.
Arguably, Astra has a slight edge on safety, with 21% of Potomac patients experiencing grade 3 or higher treatment-related adverse events, against the 29% number Pfizer reported in Crest.
Meanwhile, the Alban trial of Tecentriq plus BCG yielded 36-month EFS of 79% for both its active cohort and BCG control, resulting in a clear fail. Alban isn’t a Roche study, having been run by the French hospital network Unicancer; it has suffered delays, and until ESMO nothing was known about its outcome.
Cross-trial comparison in BCG-naive non-muscle invasive bladder cancer
| Pfizer | AstraZeneca | Roche | |
|---|---|---|---|
| Project | Sasanlimab | Imfinzi | Tecentriq |
| Study | Crest | Potomac | Alban |
| Primary endpoint | EFS | DFS | EFS |
| Combo with BCG induction + maintenance | 36mth EFS 82% | 36mth DFS 82% | 36mth EFS 79% |
| Combo with BCG induction | 36mth EFS 72% | 36mth DFS 74% | No cohort testing this |
| Control (BCG induction + maintenance) | 36mth EFS 75% | 36mth DFS 77% | 36mth EFS 79% |
| Stats for BCG i+m combo vs control | HR=0.68 (p=0.019) | HR=0.68 (p=0.015) | HR=0.98 (not stat sig) |
Source: ESMO & OncologyPipeline.
While Potomac and Crest tested a combination with BCG induction plus maintenance, they also included an exploratory cohort of PD-(L)1 plus BCG induction alone. In the case of Crest this latter cohort performed no differently to control, with a 36-month EFS number that was numerically slightly better for BCG alone.
Uncannily, this outcome was repeated in Potomac, where Imfinzi plus BCG induction yielded a 36-month DFS rate of 74%, versus 77% for BCG induction plus maintenance alone. There was no Alban cohort combining Tecentriq with BCG induction alone.
As such, neither Potomac nor Crest can boast of even being capable of reducing the need for BCG – a therapy that comes with significant inconvenience, and which has been prone to shortages. Rather, they underscore the need for patients to receive standard BCG induction and maintenance, alongside a new experimental therapy.
NMIBC has seen new drugs approved of late, but none specifically in the front-line, BCG combo setting. Merck & Co’s Keytruda is approved in post-BCG disease (based on the Keynote-057 trial), and the same goes for Johnson & Johnson’s Inlexzo, which was approved in September (Sunrise-1).
UroGen’s Zusduri was approved in June as monotherapy in BCG-naive disease, but this relates to a different setting of low-grade intermediate-risk NMIBC.
Inlexzo could, however, emerge as a competitor at some point: J&J is running the Sunrise-3 study, pitting Inlexzo monotherapy versus BCG in the same setting as Crest and Potomac, and data could come as early as next year.
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