Jeannie Hoffman-Censits: Sure. So the JAVELIN Bladder Medley trial is an international open-label randomized phase three trial, actually enrolling a special population of patients. So these are patients that had platinum-based chemotherapy and had either a complete response, a partial response, or stable disease. So it's those patients that had a clinical benefit to frontline platinum-based chemotherapy. And then those patients were randomized one-to-two to two-to-two, to Avelumab monotherapy as a control, or Avelumab plus other anti-cancer therapies. So yeah, a little bit of a complicated trial, but quite an interesting design.
Tian Zhang: And what were the treatments in those different cohorts?
Jeannie Hoffman-Censits: So it was Avelumab plus Sacituzumab, Avelumab plus an anti-TIGIT antibody, and then Avelumab plus an IL-15 inhibitor as well.
Tian Zhang: Great. So doubling down on the immune-responsive cohort.
Jeannie Hoffman-Censits: Exactly.
Tian Zhang: And what did you find?
Jeannie Hoffman-Censits: So in the primary analysis, we found that Avelumab plus Sacituzumab met the primary endpoint of improving progression-free survival. Overall survival is still premature in all of the groups, but certainly trending in the right direction. So I think showing that Avelumab plus other anti-cancer therapies in this maintenance space, kind of adding to what JAVELIN-100 has already shown, is a very interesting and reasonable strategy for those patients who've already gotten a benefit from platinum-based chemotherapy.
Tian Zhang: So special population who have already responded and they're doing the maintenance of Avelumab.
Jeannie Hoffman-Censits: Exactly.
Tian Zhang: And the Sacituzumab Govitecan with Avelumab cohort did have a little bit of improved progression-free survival. Tell us a little bit about ,as the Sacituzumab label is off the market now, so what does that look like for this combination going forward?
Jeannie Hoffman-Censits: Yeah. So Sacituzumab has had kind of an interesting history initially approved for patients with breast cancer and then an expanded label for patients with urothelial cancer. We know that those are not the same population of patients, and especially those in this trial who had previously had platinum-based chemotherapy. So one of the issues that we saw in this trial was that the toxicity was higher than expected in the Sacituzumab arm. About half the patients wound up getting growth factor. But again, in terms of improved progression-free survival, and certainly trends to overall survival, quite interesting. I'm pleased that, by guidelines, we still have Sacituzumab as a tool in our toolkit that we can use to treat patients with urothelial cancer. I think it's important, especially for those patients who don't have an enriched biomarker, like a HER2 or an FGFR3-altered tumor, we really need treatments for those patients who have, especially like EVP or platinum-refractory tumors. So I think it remains an important drug.
Tian Zhang: So more to come?
Jeannie Hoffman-Censits: Well, more to come. And I think that showing that Sacituzumab and other TROP-2-directed ADCs can be safely delivered with checkpoint inhibitors is an important message, and other similar trials are ongoing looking at those combinations as well.
Tian Zhang: Very good. Anything else you want to add for this particular trial for JAVELIN bladder medley?
Jeannie Hoffman-Censits: Well, I think the other really interesting thing about this trial that was successful is using the contemporary prospective JAVELIN-100 data as an expanded control population. I know, especially when we're talking to patients about clinical trials and all the investment that patients have to do, oftentimes if a patient is interested in going on a clinical trial, especially one where they're randomized to standard of care or standard of care plus another agent that we think may hold promise, many of those patients would rather be on the treatment arm. And because of the design, I think we were able to use that contemporary data set to expand the control arm to allow patients to have more of a chance to go on a treatment arm, which I think was pretty compelling. So hopefully more lessons can be learned from the design of this trial, which I think was really patient centered.
Tian Zhang: Sure. And we're always thinking about how do we minimize patients on a control cohort? So this is a great design way.
Jeannie Hoffman-Censits: Right.
Tian Zhang: And it helped patients maybe enroll faster. Do you think that trial enrolled faster because of that?
Jeannie Hoffman-Censits: I think certainly that is compelling to patients, and to be able to, I think, respond to some of the things that we hear, criticisms in terms of why patients may decide to pursue standard of care instead of a clinical trial. It's certainly something that we hear as a criticism to trial design. So I imagine it probably had something to do with getting that trial done.
Tian Zhang: Great. Congratulations. I'm glad to see the data here.
Jeannie Hoffman-Censits: Absolutely. Thank you.