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Emerging I-O Combination Trials in Unresectable HCC

Insights From: Richard S. Finn, MD, University of California Los Angeles
Published: Friday, Jan 31, 2020



Transcript: 

Richard S. Finn, MD: The liver cancer space is very crowded, with a lot of drug development ongoing. Certainly, most phase III studies now are concentrating on the frontline space, given that we have so many approvals in the second-line setting. As I mentioned before, there’s a big interest in combining immuno-oncology [I-O] agents with VEGF-targeted agents. IMbrave150 read out as a positive study. There’s the LEAP-002 study. This study is accruing patients and is looking at the combination of lenvatinib with pembrolizumab. The phase I/II data that were presented in 2019, at ESMO [the European Society for Medical Oncology Congress] show that with this combination, we’re getting response rates in the 30% range. Many of them are very durable. This regimen has a breakthrough therapy designation. It was recently approved in uterine cancer. So we’re very excited to see the phase III data with this combination.

Similarly, the study of durvalumab in combination with tremelimumab. This is a little different in that it’s a CTLA4 antibody in combination with a PD-L1 [programmed death-ligand 1] inhibitor. This study has completed accrual, and we’re waiting for the results. This is a study comparing the combination with sorafenib as the standard of care.

Just being launched now is the COSMIC-312 study. This is looking at cabozantinib in combination with atezolizumab. Again, this is building on this idea that VEGF inhibition and other kinase inhibition will synergize with PD-L1 inhibition. This study is just getting off the ground and is open to accrual globally.

Finally, there have also been data generated with nivolumab in combination with ipilimumab. Again, looking at this PD-1 [programmed cell death protein 1]/CTLA4 combination as a phase III study is just getting off the ground. There’s a lot of activity going on in the liver cancer space, as there has been for a decade. But at least with the IMbrave150 data we see, maybe the combinations are the future in this disease. We look forward to seeing the data from the other combinations as that data become available.

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Transcript: 

Richard S. Finn, MD: The liver cancer space is very crowded, with a lot of drug development ongoing. Certainly, most phase III studies now are concentrating on the frontline space, given that we have so many approvals in the second-line setting. As I mentioned before, there’s a big interest in combining immuno-oncology [I-O] agents with VEGF-targeted agents. IMbrave150 read out as a positive study. There’s the LEAP-002 study. This study is accruing patients and is looking at the combination of lenvatinib with pembrolizumab. The phase I/II data that were presented in 2019, at ESMO [the European Society for Medical Oncology Congress] show that with this combination, we’re getting response rates in the 30% range. Many of them are very durable. This regimen has a breakthrough therapy designation. It was recently approved in uterine cancer. So we’re very excited to see the phase III data with this combination.

Similarly, the study of durvalumab in combination with tremelimumab. This is a little different in that it’s a CTLA4 antibody in combination with a PD-L1 [programmed death-ligand 1] inhibitor. This study has completed accrual, and we’re waiting for the results. This is a study comparing the combination with sorafenib as the standard of care.

Just being launched now is the COSMIC-312 study. This is looking at cabozantinib in combination with atezolizumab. Again, this is building on this idea that VEGF inhibition and other kinase inhibition will synergize with PD-L1 inhibition. This study is just getting off the ground and is open to accrual globally.

Finally, there have also been data generated with nivolumab in combination with ipilimumab. Again, looking at this PD-1 [programmed cell death protein 1]/CTLA4 combination as a phase III study is just getting off the ground. There’s a lot of activity going on in the liver cancer space, as there has been for a decade. But at least with the IMbrave150 data we see, maybe the combinations are the future in this disease. We look forward to seeing the data from the other combinations as that data become available.

Transcript Edited for Clarity
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