CONTACT-03 Subset Analysis: Similar Cabozantinib Response Across IO Pretreatment Types - Cristina Suárez
June 13, 2025
Tian Zhang is joined by Cristina Suárez to discuss a CONTACT-03 subset analysis. CONTACT-03 was a phase III trial comparing atezolizumab plus cabozantinib versus cabozantinib monotherapy in patients with prior anti-PD-1/PD-L1 exposure that failed to meet its primary endpoints. The subset analysis focused on patients who received only first-line immunotherapy, dividing them into IO-IO versus IO-TKI groups. Unlike the CaboPoint trial, which showed higher response rates after IO-IO compared to IO-TKI, CONTACT-03 demonstrated similar response rates regardless of first-line treatment sequence. Dr. Suárez emphasizes that the key takeaway reinforces cabozantinib as an effective second-line option after any immunotherapy combination. Interestingly, duration of response appeared shorter for the atezolizumab-cabozantinib combination compared to cabozantinib monotherapy, which was unexpected and difficult to explain given the small numbers in this subset analysis.
Biographies:
Cristina Suárez, MD, PhD, Medical Oncologist, Vall d’Halbran University Hospital, Vall d’Halbron Institute of Oncology (VHIO), Barcelona, Spain
Tian Zhang, MD, MHS, Associate Professor in the Department of Internal Medicine, Associate Director of Clinical Research in the Simmons Comprehensive Cancer Center, Director of Clinical Research within the Division of Hematology and Oncology in the Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Biographies:
Cristina Suárez, MD, PhD, Medical Oncologist, Vall d’Halbran University Hospital, Vall d’Halbron Institute of Oncology (VHIO), Barcelona, Spain
Tian Zhang, MD, MHS, Associate Professor in the Department of Internal Medicine, Associate Director of Clinical Research in the Simmons Comprehensive Cancer Center, Director of Clinical Research within the Division of Hematology and Oncology in the Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Related Content:
ASCO 2025: Efficacy and Safety of Second-Line Cabozantinib +/ Atezolizumab for Patients with Advanced Renal Cell Carcinoma After Progression on Immuno-Oncology Combinations: Subgroup Analysis of CONTACT-03
No Benefit from Checkpoint Inhibitor Rechallenge: Key Findings from CONTACT-03 Trial, Journal Club - Rashid Sayyid & Zachary Klaassen
CaboPoint Trial: Cabozantinib in Second-Line RCC Treatment - Laurence Albiges
ASCO 2025: Efficacy and Safety of Second-Line Cabozantinib +/ Atezolizumab for Patients with Advanced Renal Cell Carcinoma After Progression on Immuno-Oncology Combinations: Subgroup Analysis of CONTACT-03
No Benefit from Checkpoint Inhibitor Rechallenge: Key Findings from CONTACT-03 Trial, Journal Club - Rashid Sayyid & Zachary Klaassen
CaboPoint Trial: Cabozantinib in Second-Line RCC Treatment - Laurence Albiges
Read the Full Video Transcript
Tian Zhang: Welcome to this episode of UroToday. I'm Tian Zhang, a GU medical oncologist and Associate Director of Clinical Research at UT Southwestern Medical Center in Dallas, Texas. And I'm joined today by our wonderful friend across the ocean, Dr. Cristina Suárez, a medical oncologist at the Vall d'Hebron University and Institute of Oncology in Barcelona. So happy you could be here to talk about the CONTACT-03 subset that you presented at ASCO 2025. Welcome.
Cristina Suárez: Thank you, Tian. Happy to be here.
Tian Zhang: So tell us a bit about CONTACT-03 as a trial and the initial trial and the primary outcome and then the subset analysis that you guys did.
Cristina Suárez: So the CONTACT-03 trial is a phase III trial that investigated the role of randomized patients, the role of adding atezolizumab to cabozantinib in patients that had already received anti-PD-1 or anti-PD-L1 inhibitors. So the trial randomized patients to atezolizumab plus cabozantinib versus cabozantinib.
And the two primary endpoints were progression-free survival and overall survival. And unfortunately, as you know, the trial didn't demonstrate any benefit of adding atezolizumab to cabozantinib in this setting.
Tian Zhang: Right. And so it wasn't expected to have that negative outcome. But tell us a bit more about what led to this subset analysis that you all are presenting at ASCO this year.
Cristina Suárez: So in this subset analysis, we investigated those patients that had only received first-line IO therapy. So we divided patients. We had all the population that had received first-line IO. And then we divided into IO-IO or IO-TKI.
So we didn't find any differences in the whole population that those patients that had already received first-line IO, and we didn't find any differences between IO-IO in first line versus IO-TKI. So the overall response rate was the same, and the progression-free survival was also the same.
And that was pretty different or a little bit different from the CaboPoint trial. It's the only prospective trial that we have. It's a trial that investigated the role of cabozantinib in two different cohorts. And the first cohort was patients that had already received IO-IO. Second cohort had already received an IO-TKI.
And in the CaboPoint trial, there was a difference in overall response rate. We had a 41% overall response rate after IO-IO versus 28% after IO-TKI. But we didn't find this difference in the subset analysis of CONTACT-03 trial.
Tian Zhang: So a similar response rate despite IO-IO or IO-TKI for patients on CONTACT-03.
Cristina Suárez: Yeah.
Tian Zhang: Why do you hypothesize that the response rates were similar on CONTACT-03 compared to CaboPoint?
Cristina Suárez: So I don't know the difference. The CaboPoint is a small phase II trial. So we need to see carefully that the numbers of small phase II trials. So but maybe-- I don't know. Maybe we never know why is that difference.
Tian Zhang: Some patient characteristic differences.
Cristina Suárez: Yeah.
Tian Zhang: OK. How would you apply what you're learning about the subset analysis to our current sequencing approaches?
Cristina Suárez: So I think what the subset analysis reinforces is that cabozantinib is a good second-line option anyway, whatever you have used in the first line and even IO-IO, IO-TKI. So I think that reinforce the idea of cabozantinib as a good second line after any IO combination.
Tian Zhang: From the abstract, the duration of response seemed shorter for patients on cabo with atezolizumab than for people on cabozantinib monotherapy. Why do you think that is?
Cristina Suárez: Yeah. That was pretty weird, as well. So I don't know. Maybe with these small numbers, we cannot say too much. Maybe it's a matter of numbers. But, yeah, it was pretty weird that patients in the atezo-cabo had shorter duration of response, that we always expect that the duration of response from IO.
Tian Zhang: To be longer.
Cristina Suárez: So I don't know why.
Tian Zhang: That's hard to tell. Anything else to add for our audience?
Cristina Suárez: No, I think that's the main message is that one that cabozantinib is a good second line or even third line for those patients that have been treated with immunotherapy.
Tian Zhang: Yeah, that's a great takeaway. Thank you so much. Thanks so much for having--
Cristina Suárez: Thank you very much.
Tian Zhang: --yeah, being here, and congratulations with the CONTACT-03 subset analysis.
Cristina Suárez: Thank you, Tian.
Tian Zhang: Welcome to this episode of UroToday. I'm Tian Zhang, a GU medical oncologist and Associate Director of Clinical Research at UT Southwestern Medical Center in Dallas, Texas. And I'm joined today by our wonderful friend across the ocean, Dr. Cristina Suárez, a medical oncologist at the Vall d'Hebron University and Institute of Oncology in Barcelona. So happy you could be here to talk about the CONTACT-03 subset that you presented at ASCO 2025. Welcome.
Cristina Suárez: Thank you, Tian. Happy to be here.
Tian Zhang: So tell us a bit about CONTACT-03 as a trial and the initial trial and the primary outcome and then the subset analysis that you guys did.
Cristina Suárez: So the CONTACT-03 trial is a phase III trial that investigated the role of randomized patients, the role of adding atezolizumab to cabozantinib in patients that had already received anti-PD-1 or anti-PD-L1 inhibitors. So the trial randomized patients to atezolizumab plus cabozantinib versus cabozantinib.
And the two primary endpoints were progression-free survival and overall survival. And unfortunately, as you know, the trial didn't demonstrate any benefit of adding atezolizumab to cabozantinib in this setting.
Tian Zhang: Right. And so it wasn't expected to have that negative outcome. But tell us a bit more about what led to this subset analysis that you all are presenting at ASCO this year.
Cristina Suárez: So in this subset analysis, we investigated those patients that had only received first-line IO therapy. So we divided patients. We had all the population that had received first-line IO. And then we divided into IO-IO or IO-TKI.
So we didn't find any differences in the whole population that those patients that had already received first-line IO, and we didn't find any differences between IO-IO in first line versus IO-TKI. So the overall response rate was the same, and the progression-free survival was also the same.
And that was pretty different or a little bit different from the CaboPoint trial. It's the only prospective trial that we have. It's a trial that investigated the role of cabozantinib in two different cohorts. And the first cohort was patients that had already received IO-IO. Second cohort had already received an IO-TKI.
And in the CaboPoint trial, there was a difference in overall response rate. We had a 41% overall response rate after IO-IO versus 28% after IO-TKI. But we didn't find this difference in the subset analysis of CONTACT-03 trial.
Tian Zhang: So a similar response rate despite IO-IO or IO-TKI for patients on CONTACT-03.
Cristina Suárez: Yeah.
Tian Zhang: Why do you hypothesize that the response rates were similar on CONTACT-03 compared to CaboPoint?
Cristina Suárez: So I don't know the difference. The CaboPoint is a small phase II trial. So we need to see carefully that the numbers of small phase II trials. So but maybe-- I don't know. Maybe we never know why is that difference.
Tian Zhang: Some patient characteristic differences.
Cristina Suárez: Yeah.
Tian Zhang: OK. How would you apply what you're learning about the subset analysis to our current sequencing approaches?
Cristina Suárez: So I think what the subset analysis reinforces is that cabozantinib is a good second-line option anyway, whatever you have used in the first line and even IO-IO, IO-TKI. So I think that reinforce the idea of cabozantinib as a good second line after any IO combination.
Tian Zhang: From the abstract, the duration of response seemed shorter for patients on cabo with atezolizumab than for people on cabozantinib monotherapy. Why do you think that is?
Cristina Suárez: Yeah. That was pretty weird, as well. So I don't know. Maybe with these small numbers, we cannot say too much. Maybe it's a matter of numbers. But, yeah, it was pretty weird that patients in the atezo-cabo had shorter duration of response, that we always expect that the duration of response from IO.
Tian Zhang: To be longer.
Cristina Suárez: So I don't know why.
Tian Zhang: That's hard to tell. Anything else to add for our audience?
Cristina Suárez: No, I think that's the main message is that one that cabozantinib is a good second line or even third line for those patients that have been treated with immunotherapy.
Tian Zhang: Yeah, that's a great takeaway. Thank you so much. Thanks so much for having--
Cristina Suárez: Thank you very much.
Tian Zhang: --yeah, being here, and congratulations with the CONTACT-03 subset analysis.
Cristina Suárez: Thank you, Tian.