Phase II Trial Results of Disitamab Vedotin and Toripalimab Combination for Muscle-Invasive Bladder Cancer - Xinan Sheng
March 10, 2025
Ashish Kamat speaks with Xinan Sheng about a Phase II trial evaluating disitamab vedotin (DV) combined with toripalimab for HER2-positive muscle-invasive bladder cancer. Dr. Sheng shares results showing a 63.6% pathological complete response rate among patients who underwent radical surgery following six cycles of neoadjuvant treatment. The study reveals outcomes in clinical stage T2 patients and those with HER2 3+ expression, with 12-month event-free survival reaching 92.5%. Dr. Sheng notes that adverse events were manageable, with grade 3 or higher complications occurring in only 21% of patients. Their discussion highlights that while neoadjuvant therapy is uncommon in China (used in just 5% of MIBC patients versus 20-40% in Western countries), this promising ADC-immunotherapy combination is already gaining traction among Chinese urologists and patients who typically avoid traditional chemotherapy, potentially shifting treatment paradigms for the 20-40% of patients who test positive for HER2 expression.
Biographies:
Xinan Sheng, MD, Deputy Director, Department of Genitourinary Oncology, Peking University Cancer Hospital, Beijing, China
Ashish Kamat, MD, MBBS, Professor of Urology and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX
Biographies:
Xinan Sheng, MD, Deputy Director, Department of Genitourinary Oncology, Peking University Cancer Hospital, Beijing, China
Ashish Kamat, MD, MBBS, Professor of Urology and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX
Related Content:
ASCO GU 2025: Neoadjuvant Treatment with Disitamab Vedotin plus Perioperative Toripalimab in Patients with MIBC with HER2 Expression: Updated Efficacy and Safety Results from the Phase II RC48-C017 Trial
ASCO GU 2025: Discussant: Advancements in Urothelial Cancer Perioperative Therapy
ASCO GU 2025: Neoadjuvant Treatment with Disitamab Vedotin plus Perioperative Toripalimab in Patients with MIBC with HER2 Expression: Updated Efficacy and Safety Results from the Phase II RC48-C017 Trial
ASCO GU 2025: Discussant: Advancements in Urothelial Cancer Perioperative Therapy
Read the Full Video Transcript
Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center. We're live in San Francisco for ASCO GU 25. It's my pleasure to welcome to the studios Professor Xinan Sheng, who's going to talk to us today about the abstract that he's presenting here at GU ASCO on DV in the neoadjuvant space. So, Professor, tell us the data.
Xinan Sheng: Yeah, thank you. I'm pleased to talk about our study. Our study is a phase II trial, and it’s to evaluate the efficacy and the safety of DV combined with toripalimab, a PD-1 antibody, for muscle-invasive bladder cancer with HER2 expression.
This study enrolled 47 patients who received the neoadjuvant treatment. Eligible patients for radical surgery with HER2 expression received DV combined with toripalimab for six cycles, followed by the radical surgery. After surgery, they received toripalimab as adjuvant treatment for a total of one year. Our study’s primary endpoint is pathological complete response rate. The secondary endpoints include event-free survival, overall survival, and safety.
By the cutoff data, 47 patients received the neoadjuvant treatment, and 33 patients received the radical surgery. Fourteen patients did not receive the radical surgery. Among all of them, two patients developed distant metastases. One patient did not recover from the adverse event within the operative window and then received a TURBT and achieved T0. Among 11 patients, eight patients received the TURBT treatment, and five patients completely achieved T0.
Our patients are in—the patients who received the radical surgery: 21 patients achieved the pathological complete response. So for the primary endpoint, the pathological complete response rate is 63.6%. Two patients achieved a partial response. So for the chart, the total partial response rate is 25%.
Subgroup analysis showed that for the patients who are clinical stage T2, it’s higher than the other subgroup. T2 patients account for 40%. The PCR rate was 8—maybe about 8% to 5%. For the biomarker analysis, we showed that for the patient who has HER2 3+, using a new molecularly higher than HER2 1+ and 2+ subgroup, regardless of PD-L1 expression, two patients that have the HER2 3+ and PD-L1 expression positive, the PCR rate is 100%. Yeah, two patients and the complete response rate.
So for the event-free survival with a median 14-month follow-up, the 12-month EFS rate is 92.5%, and the median is not reached. For the total ITT patients, the median EFS is not reached. For the ITT patients, the EFS rate is about 19%. So now you know the median overall survival is not reached.
About safety, for the postoperative complications, most are mild. Just two patients had a grade 3 complication. For all patients, including neoadjuvant and adjuvant treatment, grade 3 and above adverse events account for just 21%. So we think the safety was very manageable.
So, in conclusion, this trial is the first prospective study to show that a PD-1 antibody combined with an ADC drug for neoadjuvant therapy in MIBC has shown us promising efficacy. Maybe we need more data, more follow-up, and to try to evaluate the PD-1 antibody combined with ADC drugs for MIBC. Maybe CCR EV-304 trials, the two phase III trials, will publish those data. Yeah.
Ashish Kamat: Right now. Thank you so much. Very impressive how you remember all these numbers without a slide, and we're just talking. It is very striking that you had such high path CR rates in these patients, and this makes us think that these patients might be able to save their bladders. Do you have any studies planned for bladder preservation?
Xinan Sheng: No, no.
Ashish Kamat: Because that's something, of course, we can't tell from this study, but for the patients who are looking at the path CR, how it correlates with clinical complete response—that would be the logical next step for these patients as well. And how about the paradigm right now when you see a patient in your clinic—are you now switching based on your results to ADC and PD-1, or are you still doing platinum-based neoadjuvant chemotherapy?
Xinan Sheng: In China, fewer patients receive neoadjuvant therapy. Most urologists and most patients like to do surgery once MIBC is diagnosed. But not the radical cystectomy—just maybe many, many TURBTs. After that, we give patients an adjuvant treatment. Yeah. So maybe just 5% of MIBC patients would receive neoadjuvant chemotherapy.
Ashish Kamat: 5% is very low.
Xinan Sheng: Yeah. We know in the USA or in Western countries, maybe 20% to 40%.
Ashish Kamat: So do you think this paradigm with the data from your trial will convince more urologists to use neoadjuvant therapy?
Xinan Sheng: I think so. Our data—last ASCO meeting, we presented our data by poster. So in this half year, many, many urologists gave patients this PD-1 plus DV for the HER2 expression patients in the neoadjuvant setting—maybe more than 5% or 10%. Yeah. In China, most patients don't like chemo, so for the PD antibody or ADC drug, many patients like to receive the treatment just two or three weeks, just give one dose, and the safety was well manageable. So more and more patients maybe receive this combination to give neoadjuvant to them.
Ashish Kamat: Right. Now, what is the prevalence of HER2 positivity in the Chinese population? How many patients do you have to screen to be able to select patients for the treatment?
Xinan Sheng: Now, in China—in the Chinese guideline for UC patients, we test every patient for HER2 expression. Actually, our data show that HER2-positive is about 20% to 40%. We define HER2+ or 3+ as positive—not the breast cancer HER2-positive criterion. In the T-DXd trial, maybe in that trial they define HER2 3+ or FISH-positive as HER2-positive. There’s a difference.
Ashish Kamat: Well, thank you so much. Congratulations on excellent results, and thank you for taking the time and spending it with us.
Xinan Sheng: Thank you. Yeah.
Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center. We're live in San Francisco for ASCO GU 25. It's my pleasure to welcome to the studios Professor Xinan Sheng, who's going to talk to us today about the abstract that he's presenting here at GU ASCO on DV in the neoadjuvant space. So, Professor, tell us the data.
Xinan Sheng: Yeah, thank you. I'm pleased to talk about our study. Our study is a phase II trial, and it’s to evaluate the efficacy and the safety of DV combined with toripalimab, a PD-1 antibody, for muscle-invasive bladder cancer with HER2 expression.
This study enrolled 47 patients who received the neoadjuvant treatment. Eligible patients for radical surgery with HER2 expression received DV combined with toripalimab for six cycles, followed by the radical surgery. After surgery, they received toripalimab as adjuvant treatment for a total of one year. Our study’s primary endpoint is pathological complete response rate. The secondary endpoints include event-free survival, overall survival, and safety.
By the cutoff data, 47 patients received the neoadjuvant treatment, and 33 patients received the radical surgery. Fourteen patients did not receive the radical surgery. Among all of them, two patients developed distant metastases. One patient did not recover from the adverse event within the operative window and then received a TURBT and achieved T0. Among 11 patients, eight patients received the TURBT treatment, and five patients completely achieved T0.
Our patients are in—the patients who received the radical surgery: 21 patients achieved the pathological complete response. So for the primary endpoint, the pathological complete response rate is 63.6%. Two patients achieved a partial response. So for the chart, the total partial response rate is 25%.
Subgroup analysis showed that for the patients who are clinical stage T2, it’s higher than the other subgroup. T2 patients account for 40%. The PCR rate was 8—maybe about 8% to 5%. For the biomarker analysis, we showed that for the patient who has HER2 3+, using a new molecularly higher than HER2 1+ and 2+ subgroup, regardless of PD-L1 expression, two patients that have the HER2 3+ and PD-L1 expression positive, the PCR rate is 100%. Yeah, two patients and the complete response rate.
So for the event-free survival with a median 14-month follow-up, the 12-month EFS rate is 92.5%, and the median is not reached. For the total ITT patients, the median EFS is not reached. For the ITT patients, the EFS rate is about 19%. So now you know the median overall survival is not reached.
About safety, for the postoperative complications, most are mild. Just two patients had a grade 3 complication. For all patients, including neoadjuvant and adjuvant treatment, grade 3 and above adverse events account for just 21%. So we think the safety was very manageable.
So, in conclusion, this trial is the first prospective study to show that a PD-1 antibody combined with an ADC drug for neoadjuvant therapy in MIBC has shown us promising efficacy. Maybe we need more data, more follow-up, and to try to evaluate the PD-1 antibody combined with ADC drugs for MIBC. Maybe CCR EV-304 trials, the two phase III trials, will publish those data. Yeah.
Ashish Kamat: Right now. Thank you so much. Very impressive how you remember all these numbers without a slide, and we're just talking. It is very striking that you had such high path CR rates in these patients, and this makes us think that these patients might be able to save their bladders. Do you have any studies planned for bladder preservation?
Xinan Sheng: No, no.
Ashish Kamat: Because that's something, of course, we can't tell from this study, but for the patients who are looking at the path CR, how it correlates with clinical complete response—that would be the logical next step for these patients as well. And how about the paradigm right now when you see a patient in your clinic—are you now switching based on your results to ADC and PD-1, or are you still doing platinum-based neoadjuvant chemotherapy?
Xinan Sheng: In China, fewer patients receive neoadjuvant therapy. Most urologists and most patients like to do surgery once MIBC is diagnosed. But not the radical cystectomy—just maybe many, many TURBTs. After that, we give patients an adjuvant treatment. Yeah. So maybe just 5% of MIBC patients would receive neoadjuvant chemotherapy.
Ashish Kamat: 5% is very low.
Xinan Sheng: Yeah. We know in the USA or in Western countries, maybe 20% to 40%.
Ashish Kamat: So do you think this paradigm with the data from your trial will convince more urologists to use neoadjuvant therapy?
Xinan Sheng: I think so. Our data—last ASCO meeting, we presented our data by poster. So in this half year, many, many urologists gave patients this PD-1 plus DV for the HER2 expression patients in the neoadjuvant setting—maybe more than 5% or 10%. Yeah. In China, most patients don't like chemo, so for the PD antibody or ADC drug, many patients like to receive the treatment just two or three weeks, just give one dose, and the safety was well manageable. So more and more patients maybe receive this combination to give neoadjuvant to them.
Ashish Kamat: Right. Now, what is the prevalence of HER2 positivity in the Chinese population? How many patients do you have to screen to be able to select patients for the treatment?
Xinan Sheng: Now, in China—in the Chinese guideline for UC patients, we test every patient for HER2 expression. Actually, our data show that HER2-positive is about 20% to 40%. We define HER2+ or 3+ as positive—not the breast cancer HER2-positive criterion. In the T-DXd trial, maybe in that trial they define HER2 3+ or FISH-positive as HER2-positive. There’s a difference.
Ashish Kamat: Well, thank you so much. Congratulations on excellent results, and thank you for taking the time and spending it with us.
Xinan Sheng: Thank you. Yeah.