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COSMIC-312 Trial Overview

Panelists: Ghassan K. Abou-Alfa, MD, MBA, Memorial Sloan Kettering Cancer Center; Anthony B. El-Khoueiry, MD, Southern California Clinical and Translational Science Institute; Catherine T. Frenette, MD, MD Anderson Cancer Center; Pierre Gholam, MD, UH Westlake Health Center; Ahmed Kaseb, MD, MD Anderson Cancer Center
Published: Thursday, Mar 26, 2020



Transcript:

Ghassan K. Abou-Alfa, MD, MBA: Anthony, I would like to wrap this up 1 more time because you brought up the COSMIC-312 trial, and we discussed that a little. I’m a little lost here. Tell us, because if I do recall, the design of the study is the combination versus single-agent CABO [cabozantinib] versus single-agent sorafenib. Tell us a little bit; you can maybe take that a little further.

Anthony B. El-Khoueiry, MD: Sure. At the time this trial was designed, sorafenib was the standard for first-line therapy, so that’s the control arm. Cabozantinib is another multitargeted tyrosine kinase inhibitor with some unique targets. In addition to targeting the VEGF axis, it targets a Met, which is the receptor to hepatocyte growth factor. It targets AXL, it targets miR [micro RNA]. There is actually very nice preclinical scientific evidence about having immunomodulatory effects. It provides stronger rationale to combining it with atezolizumab. Then there is an arm exploring cabozantinib as a single agent to separate whether the combination is really providing at least additive or maybe synergistic affects versus cabozantinib alone. So that’s the idea of the 3-arm trial.

Ghassan K. Abou-Alfa, MD, MBA: Yeah, I admit that the “potential confusion” is because CABO [cabozantinib] is more understood as a second-line therapy, and now we’re hearing it being in a first-line setting with CABO-ATEZO [cabozantinib-atezolizumab] versus CABO [cabozantinib]. But I think Dr El-Khoueiry explained it to us very clearly. After all, it’s really about understanding what the contribution is of the CABO [cabozantinib] as single agent compared with the ATEZO-CABO [atezolizumab-cabozantinib]. But I would say this is a very exciting field. None of us can really say where this is going to take us. As we can see, the data are evolving very quick, and we have many critical trials that are yet to be reported in regard to first-line therapy. If anything, at the moment we have ATEZO-BEV [atezolizumab-bevacizumab] as we heard, and we summarized that data for you. Of course, we are waiting still for the PEMBRO [pembrolizumab] plus lenvatinib. We’re waiting for the ATEZO plus cabozantinib. We’re waiting for the durvalumab plus tremelimumab.

We’re opening in combination also with regorafenib. There are lots of them. And I have to say, we just have to wait and see. If anything, it’s good news that we have that wealth of information.

Transcript Edited for Clarity

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Transcript:

Ghassan K. Abou-Alfa, MD, MBA: Anthony, I would like to wrap this up 1 more time because you brought up the COSMIC-312 trial, and we discussed that a little. I’m a little lost here. Tell us, because if I do recall, the design of the study is the combination versus single-agent CABO [cabozantinib] versus single-agent sorafenib. Tell us a little bit; you can maybe take that a little further.

Anthony B. El-Khoueiry, MD: Sure. At the time this trial was designed, sorafenib was the standard for first-line therapy, so that’s the control arm. Cabozantinib is another multitargeted tyrosine kinase inhibitor with some unique targets. In addition to targeting the VEGF axis, it targets a Met, which is the receptor to hepatocyte growth factor. It targets AXL, it targets miR [micro RNA]. There is actually very nice preclinical scientific evidence about having immunomodulatory effects. It provides stronger rationale to combining it with atezolizumab. Then there is an arm exploring cabozantinib as a single agent to separate whether the combination is really providing at least additive or maybe synergistic affects versus cabozantinib alone. So that’s the idea of the 3-arm trial.

Ghassan K. Abou-Alfa, MD, MBA: Yeah, I admit that the “potential confusion” is because CABO [cabozantinib] is more understood as a second-line therapy, and now we’re hearing it being in a first-line setting with CABO-ATEZO [cabozantinib-atezolizumab] versus CABO [cabozantinib]. But I think Dr El-Khoueiry explained it to us very clearly. After all, it’s really about understanding what the contribution is of the CABO [cabozantinib] as single agent compared with the ATEZO-CABO [atezolizumab-cabozantinib]. But I would say this is a very exciting field. None of us can really say where this is going to take us. As we can see, the data are evolving very quick, and we have many critical trials that are yet to be reported in regard to first-line therapy. If anything, at the moment we have ATEZO-BEV [atezolizumab-bevacizumab] as we heard, and we summarized that data for you. Of course, we are waiting still for the PEMBRO [pembrolizumab] plus lenvatinib. We’re waiting for the ATEZO plus cabozantinib. We’re waiting for the durvalumab plus tremelimumab.

We’re opening in combination also with regorafenib. There are lots of them. And I have to say, we just have to wait and see. If anything, it’s good news that we have that wealth of information.

Transcript Edited for Clarity
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