Trial Explores Nab-paclitaxel/Nivolumab Combination in Cisplatin-Ineligible Bladder Cancer - Chiara Mercinelli
July 14, 2025
Zachary Klaassen discusses the NureCombo Trial with Chiara Mercinelli, examining neoadjuvant therapy for muscle-invasive bladder cancer. This phase II trial investigated nab-paclitaxel plus nivolumab for cisplatin-ineligible patients, delivering four cycles before cystectomy followed by one year of adjuvant nivolumab. The study achieved a 32% pathological complete response rate with 89% overall survival at 24 months median follow-up. Transcriptomic analysis revealed that non-luminal molecular subtypes and immune-related signatures correlated with higher PCR rates, potentially identifying biomarkers for immunotherapy benefit. Dr. Mercinelli acknowledges the rapidly evolving landscape, noting the challenge of designing future trials given emerging data from NIAGARA and pembrolizumab-enfortumab vedotin combinations. The discussion emphasizes the need for better patient selection strategies and clinical complete response definitions to potentially avoid radical cystectomy in appropriately selected patients, representing the ongoing evolution toward personalized bladder cancer treatment.
Biographies:
Chiara Mercinelli, GU Medical Oncologist, IRCCS San Raffaele Hospital, Milan, Italy
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Chiara Mercinelli, GU Medical Oncologist, IRCCS San Raffaele Hospital, Milan, Italy
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Related Content:
IBCN 2024: Circulating Immune-Modulators of Response to Neoadjuvant Nivolumab + Nab-Paclitaxel in Muscle Invasive Bladder Cancer: Biomarker Analyses from Nure-COMBO Trial
EAU 2025: NIAGARA: Surgical Outcomes and Neoadjuvant Safety with Perioperative Durvalumab for Muscle-Invasive Bladder Cancer
IBCN 2024: Circulating Immune-Modulators of Response to Neoadjuvant Nivolumab + Nab-Paclitaxel in Muscle Invasive Bladder Cancer: Biomarker Analyses from Nure-COMBO Trial
EAU 2025: NIAGARA: Surgical Outcomes and Neoadjuvant Safety with Perioperative Durvalumab for Muscle-Invasive Bladder Cancer
Read the Full Video Transcript
Zachary Klaassen: Hi. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We're in Chicago for ASCO 2025. On UroToday, I'm delighted to be joined by Dr. Chiara Mercinelli, who is a medical oncologist at San Raffaele in Milan, Italy. Chiara, thanks for joining us on UroToday.
Chiara Mercinelli: Thank you for having me here today.
Zachary Klaassen: Absolutely. And we're going to talk about the NureCombo Trial, which is a phase II trial. Before we get into that, the neoadjuvant adjuvant space, we've seen a lot of activity in the last couple of years, maybe just a high-level overview and where this trial potentially fit in the rationale for the trial.
Chiara Mercinelli: Well, of course, what we know is that by now the standard is still represented by cisplatin-gemcitabine. Of course, now plus immunotherapy after the NIAGARA study. But our idea was to try to find a combination, try to include all the patients who are cisplatin ineligible. So for this reason, we designed a trial with nab-paclitaxel as a chemotherapy backbone in combination with nivolumab.
Zachary Klaassen: Excellent. Just tell us a little bit about the intervention. Maybe some of the eligibility criteria for this trial.
Chiara Mercinelli: Yes, of course. All patients were diagnosed with muscle-invasive bladder cancer, mostly with urothelial carcinoma. So it must be more than 50% of urothelial carcinoma. And they were cisplatin ineligible or most of them refused cisplatin. And so try to get the immunotherapy within our trial.
Zachary Klaassen: How many doses before cystectomy were you guys looking at?
Chiara Mercinelli: It was four doses of combination of nivolumab and paclitaxel before radical cystectomy, and then one year of adjuvant nivolumab alone.
Zachary Klaassen: OK. Excellent. And so I know you've presented results already. I've some interesting biomarker data that you presented this week and a little bit of the overall survival updates. Maybe tell us about those results.
Chiara Mercinelli: Yes, of course. Well, as you told the main work is already published. And we obtain a 32% of pathological complete response rate. After more than 24 months of median follow-up, we obtain a very interesting also efficacy results with 89% of patients alive after 24 months.
Zachary Klaassen: Excellent.
Chiara Mercinelli: And also in the present abstract, we present the data of a transcriptomic analysis made in collaboration with parasites. So we identified the different molecular subtypes, in particular the non luminal one, where those associated with the higher PCR rate. And also there were some immune-related signatures that were, too, associated with the PCR.
So it is changing maybe the kind of biomarker that we need to find to define the patients who really can benefit from immunotherapy.
Zachary Klaassen: Absolutely. So in this very fast-moving disease space that we hit on in the beginning, how does this data fit into maybe clinical practice or even designing future clinical trials?
Chiara Mercinelli: Our first intention was to design a phase III trial. We do not exclude this possibility. But, of course, now, everything is quickly changing, as you mentioned. And, of course, we cannot ignore the excellent results of pembro-EV that we obtained as a first line. So, of course, with the results that are arriving also in the adjuvant setting, we are waiting to see if something is going to change and to substitute the cisplatin-gemcitabine backbone.
Zachary Klaassen: Excellent.
Chiara Mercinelli: So there is space, I think, for this kind of combination, but it is quite a difficult moment.
Zachary Klaassen: It's almost-- not an embarrassment of riches. But we're starting to see a lot of activity, which is great for our patients, great for us as providers to be able to offer these options. So any other take-home points from the NureCombo Trial, anything we haven't hit on yet?
Chiara Mercinelli: Well, other thing that we've done in the NureCombo Trial and in other trials that are currently ongoing in our hospital is trying to somehow define the clinical complete response, and so try to avoid the radical cystectomy. In particular, in NureCombo, only three patients reached that.
And I think that the new trials need not only to find a good combination that could obtain an excellent outcomes, but also try to focus on how to select the patients in order to try to avoid this major surgery.
Zachary Klaassen: Yeah. Great points. Awesome discussion on your combo. Thanks for joining us on UroToday.
Chiara Mercinelli: Thank you very much.
Zachary Klaassen: Hi. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We're in Chicago for ASCO 2025. On UroToday, I'm delighted to be joined by Dr. Chiara Mercinelli, who is a medical oncologist at San Raffaele in Milan, Italy. Chiara, thanks for joining us on UroToday.
Chiara Mercinelli: Thank you for having me here today.
Zachary Klaassen: Absolutely. And we're going to talk about the NureCombo Trial, which is a phase II trial. Before we get into that, the neoadjuvant adjuvant space, we've seen a lot of activity in the last couple of years, maybe just a high-level overview and where this trial potentially fit in the rationale for the trial.
Chiara Mercinelli: Well, of course, what we know is that by now the standard is still represented by cisplatin-gemcitabine. Of course, now plus immunotherapy after the NIAGARA study. But our idea was to try to find a combination, try to include all the patients who are cisplatin ineligible. So for this reason, we designed a trial with nab-paclitaxel as a chemotherapy backbone in combination with nivolumab.
Zachary Klaassen: Excellent. Just tell us a little bit about the intervention. Maybe some of the eligibility criteria for this trial.
Chiara Mercinelli: Yes, of course. All patients were diagnosed with muscle-invasive bladder cancer, mostly with urothelial carcinoma. So it must be more than 50% of urothelial carcinoma. And they were cisplatin ineligible or most of them refused cisplatin. And so try to get the immunotherapy within our trial.
Zachary Klaassen: How many doses before cystectomy were you guys looking at?
Chiara Mercinelli: It was four doses of combination of nivolumab and paclitaxel before radical cystectomy, and then one year of adjuvant nivolumab alone.
Zachary Klaassen: OK. Excellent. And so I know you've presented results already. I've some interesting biomarker data that you presented this week and a little bit of the overall survival updates. Maybe tell us about those results.
Chiara Mercinelli: Yes, of course. Well, as you told the main work is already published. And we obtain a 32% of pathological complete response rate. After more than 24 months of median follow-up, we obtain a very interesting also efficacy results with 89% of patients alive after 24 months.
Zachary Klaassen: Excellent.
Chiara Mercinelli: And also in the present abstract, we present the data of a transcriptomic analysis made in collaboration with parasites. So we identified the different molecular subtypes, in particular the non luminal one, where those associated with the higher PCR rate. And also there were some immune-related signatures that were, too, associated with the PCR.
So it is changing maybe the kind of biomarker that we need to find to define the patients who really can benefit from immunotherapy.
Zachary Klaassen: Absolutely. So in this very fast-moving disease space that we hit on in the beginning, how does this data fit into maybe clinical practice or even designing future clinical trials?
Chiara Mercinelli: Our first intention was to design a phase III trial. We do not exclude this possibility. But, of course, now, everything is quickly changing, as you mentioned. And, of course, we cannot ignore the excellent results of pembro-EV that we obtained as a first line. So, of course, with the results that are arriving also in the adjuvant setting, we are waiting to see if something is going to change and to substitute the cisplatin-gemcitabine backbone.
Zachary Klaassen: Excellent.
Chiara Mercinelli: So there is space, I think, for this kind of combination, but it is quite a difficult moment.
Zachary Klaassen: It's almost-- not an embarrassment of riches. But we're starting to see a lot of activity, which is great for our patients, great for us as providers to be able to offer these options. So any other take-home points from the NureCombo Trial, anything we haven't hit on yet?
Chiara Mercinelli: Well, other thing that we've done in the NureCombo Trial and in other trials that are currently ongoing in our hospital is trying to somehow define the clinical complete response, and so try to avoid the radical cystectomy. In particular, in NureCombo, only three patients reached that.
And I think that the new trials need not only to find a good combination that could obtain an excellent outcomes, but also try to focus on how to select the patients in order to try to avoid this major surgery.
Zachary Klaassen: Yeah. Great points. Awesome discussion on your combo. Thanks for joining us on UroToday.
Chiara Mercinelli: Thank you very much.