Phase II Trial for BCG Unresponsive Non-Muscle Invasive Bladder Cancer - Michael Woods

April 12, 2021

Joining Alicia Morgans, MD, MPH, is Michael Woods, MD, who is the leader of the Alliance trial A031803, a phase II trial studying how well gemcitabine with pembrolizumab works in treating patients with non-muscle invasive bladder cancer (NMIBC) who are unresponsive to bacillus Calmette-Guérin (BCG). This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for a longer period compared to gemcitabine alone. The results of the A031803 trial will provide insights into novel treatment approaches in this patient population and support the importance of additional research combining intravesical therapy with immune checkpoint inhibition.


Michael Woods, MD, Professor, Department of Urology, Loyola University Medical Center, Chicago, Illinois

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today, Dr. Michael Woods, who is a Professor of Urology at Loyola University Medical Center, also in Chicago. Thank you so much for being here with me today, Dr. Woods.

Michael Woods: Dr. Morgans, thank you so much for having me. I'm very excited to be with you today.

Alicia Morgans: Wonderful. I wanted to talk with you about a really exciting Alliance trial that you were leading, A031803, which is a phase two trial for patients who have BCG unresponsive non-muscle invasive bladder cancer. Before we get started really digging into the patient population and the schema, can you tell me a little bit about this clinical population? The population of patients who has BCG unresponsive disease?

Michael Woods: Sure. Bladder cancer is one of the most common cancers that we face as urological oncologists, and the mainstay for treatment for people with the high-grade disease is BCG. We run into an issue when the BCG no longer is responsive and patients are often left with facing, going on to undergoing a radical cystectomy, and cystectomies, bladder removal, have a significant change in lifestyle and morbidity for patients. And so, one of the unmet needs in urologic oncology is finding alternative therapies to prevent, or at least delay, patients going on to radical cystectomy.

Alicia Morgans: Absolutely. And so, if that's the population, what is the trial? What are you proposing and what are you doing in this Alliance study?

Michael Woods: So what we are looking at is one of the treatments that's been used for patients in this situation is intravesical gemcitabine. And it does have some activity, but the dermal responses are fairly low. And so, what we're looking at is the use of one of the new checkpoint inhibitors, pembrolizumab, which has been demonstrated to have activity in bladder cancer. Initially, it was shown to be successful in more advanced diseases, which you know very well, you treat these patients. And there have been many efforts in urologic oncology to move this drug earlier in the treatment. And so, what we are using is some of the exciting results that came out of KEYNOTE-057, which showed that pembrolizumab alone did have activity in this patient population. So we're using this in combination with gemcitabine to see if we can more improve these outcomes and help this population of patients.

Alicia Morgans: I just think that's such an exciting approach because as you said, pembrolizumab has activity alone. Gemcitabine has some good activity on its own. The synergy between the two, perhaps by the stimulation of neoantigen presentation with the gemcitabine and really having that pembro in there, I just think that is a fantastic approach. So I think your rationale is great. What does treatment look like for patients?

Michael Woods: So the way that we've designed this study is that the treatment for gemcitabine is based on one of the SWOG studies from many years ago, where they would receive a six-week induction course of gemcitabine followed by monthly maintenance. And so, we've used the current dosing when the trial was designed, which was pembrolizumab every three weeks. So the way we've designed it is that patients will get the standard induction gemcitabine for six weeks and they then receive the pembrolizumab every three weeks. And then once patients have a response and they enter a maintenance phase, they would get the gemcitabine and pembrolizumab every three weeks. We changed the gemcitabine dosing to allow for patient convenience, so they would come in just for one visit to receive both medications.

Alicia Morgans: Great. And how long does the ongoing treatment though with the pembrolizumab go over the course of the study?

Michael Woods: They receive both therapies for up to one year.

Alicia Morgans: Okay. Wow. So really for those patients who are high risk as this population often is, and they really just want to nip it in the bud, I think it is a fantastic approach and really building off of quite a bit of positive data as it is. So what are the primary endpoints for the trial?

Michael Woods: So we have designed the trial with two primary endpoints. The first one is patients who have carcinoma in situ in their pathology. And those patients can have papillary disease as well if you are in high-grade TA or T1. In those patients, we would look at that subgroup and look for a complete response at six months. We like to use CAS as a marker for complete response in this population. The other endpoint will be a 16-month event-free survival. We will actually include patients who have just papillary disease, either TA or T1. And then we would look at the whole group together and see what the event-free rate is at 18 months. It's one of the benefits of the trial is that you can enroll patients who don't have carcinoma in situ.

Alicia Morgans: That's fantastic. So it really just allows that extra group in there. And at this point, how many patients have you enrolled more or less?

Michael Woods: So we currently have 16 patients enrolled, and our overall goal for accrual is 161 patients.

Alicia Morgans: Wow. So how many sites do you actually have open that can help to enroll all of these patients?

Michael Woods: Right now, it's approximately 300.

Alicia Morgans: That's fantastic. What that says to me is that patients no matter where they are, hopefully, will have access to one of the sites in their relatively local area to potentially get involved in this study and hopefully, have a good outcome, save their bladder. And 300 sites is a phenomenal number. So in order to really facilitate that, we're certainly going to have information from up on the website here so that patients can find sites. And Michael, are you available for people to contact if they are interested in this trial?

Michael Woods: I'd be happy to. If anyone wants to reach out to me to help facilitate opening a trial or have any questions about the trial, probably the best way to reach me is by email. And that is .

Alicia Morgans: Great. And we will make sure that that is available in print also on our site. We will also have a schema document so that people can see, or picture so that people can see how these patients are going to be treated and just get a gestalt of what that therapy looks like. Michael, if you had to give a concluding recommendation thought about this trial, what would your thought be?

Michael Woods: Well, what I would say is that this is an unmet need in urology, and there are several different pharma companies and investigators looking at different ways to approach this disease. And I would say that one of the reasons that drove me to this design of this trial is that it uses drugs that we are familiar with as urologists and as medical oncologists. And I think that allows a lot of flexibility for providers to offer this talk of this treatment.

Alicia Morgans: And a lot of reassurance, I think too. When we feel comfortable with something, when we know that there are positive data out there, I think it always helps us to feel confident to put our patients on these trials and for patients to really commit to and get engaged. And patients on clinical trials always do better, even when they are receiving the same treatments as the standard of care, this is something that we have seen as well. So I encourage patients who are listening and who are thinking about these things to reach out and get connected and participate in this trial or in other trials because I do think that it can improve your outcomes and help you live longer, feel better and really help you engage with the community, even on that other level. Thank you so much for your time today, Dr. Woods. We look forward to hearing updates about this trial as more and more patients get involved and best of luck to you and your team.

Michael Woods: All right. Thank you very much, Alicia and to UroToday for having me.