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IDO Inhibitors for Melanoma

Panelists: Jeffrey Weber, MD, PhD, NYU Langone Medical Center; Reinhard Dummer, MD, University of Zurich Hospital;Axel Hauschild, MD, University of Kiel;Caroline Robert, MD, PhD, Gustave Roussy; Dirk Schadendorf, MD, University Hospital Essen
Published: Monday, Jan 23, 2017


Transcript:

Jeffrey Weber, MD, PhD:
Reinhard, what about IDO inhibitors, epacadostat/pembrolizumab? I thought that looked awfully encouraging.

Reinhard Dummer, MD: Yes, I was really impressed by these data, and from both sides. First, from the efficacy and second, by the tolerability. This seems to be a promising approach, and you have to keep in mind that the monotherapy with the IDO1 inhibitor is more or less without any clinical benefit. There is really the hope that, together with the anti-PD-1 strategy, this will be promising. Well, it was quite a step to jump directly from the phase I into the phase III clinical trial. But, on the other hand, without a phase III clinical trial, we will never know. So, if you investigate this with these data, you have to do so in the right way, which is phase III. Additional phase II, I think, would not happen.

Jeffrey Weber, MD, PhD: It almost makes you want to have an early look, meaning, have a phase III design, and those designs exist where you can have an early look, almost like a randomized phase II trial. And then, if it looks good enough, you jump on to the big phase III, but you can include the earlier data within the total analysis.

Caroline Robert, MD, PhD: Exactly.

Axel Hauschild, MD: But the phase III is already activated; the trial is running already. They’re actively recruiting.

Dirk Schadendorf, MD: And recruiting like crazy.

Jeffrey Weber, MD, PhD: Yes, that’s the problem. If it recruits quickly, you can’t do that.

Axel Hauschild, MD: I was surprised when Reinhard was telling us about his biomarker panel in Zurich. Because he was including IDO1, already, as one of the biomarkers. IDO1, to my best knowledge, is a prognostic marker for melanoma. In fact, it is prognostic. But is it a prognostic and predictive marker?

Reinhard Dummer, MD: We don’t know, but we have it in our immunohistochemistry panel and we see stainings; the stainings work very nicely. We have some questions with the interpretation because the stains that stain mostly are endothelial cells.

Jeffrey Weber, MD, PhD: We’re getting close to the end. This has been incredibly informative. But before we end this outstanding discussion with 4 great colleagues, I’d like to get final thoughts from each of the panelists. So, Reinhard, Dr. Dummer, what’s your final thought to wrap things up?

Reinhard Dummer, MD: We live in exciting times! We are privileged that we are in this. And we have a lot to do. I think this is a great opportunity for academia to create developments that will help our patients.

Jeffrey Weber, MD, PhD: Axel, Dr. Hauschild?

Axel Hauschild, MD: Just like the other panelists, I have been in the field for more than 20 years and I had numerous clinical trials that failed to demonstrate even a response rate difference. So, it’s fantastic to see all these clinical trials coming up and 8 new drugs approved in just 5 years. I believe the future lies in combinational and sequential approaches, which are intelligent, and only biomarker studies can help us to distinguish the best schedule from a schedule that is likely to be as efficacious.

Jeffrey Weber, MD, PhD: Caroline, Dr. Robert?

Caroline Robert, MD, PhD: Yes, I agree. And I think the ground is moving under our feet. We have new drugs, new toxicity to manage, new classification for the RECIST, and new classification for the melanoma is going to arrive. So, we have to do frequent dates like that. And it was not Peer Exchange®, it was Legend of the Fall think.

Jeffrey Weber, MD, PhD: Okay. And Dirk, Dr. Schadendorf?

Dirk Schadendorf, MD: So, I think we have come, over the last 5 or 6 years, from a graveyard to close to heaven now. I think this is a transformation, which is unmatched and unseen. I was afraid that, after all the successful trials and drugs now available, that there would not be enough interest to keep the science and the development going. And I’m pleased to see that so many more companies and drugs and drug combinations are being tested now in the field of melanoma, actually paving the way for targeted therapy as well as for our checkpoint blockade in other fields of oncology. This is very gratifying.

Jeffrey Weber, MD, PhD: Great. So, thanks to all of you for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this Peer Exchange® discussion to be useful and informative. Thank you very much.

Transcript Edited for Clarity
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Transcript:

Jeffrey Weber, MD, PhD:
Reinhard, what about IDO inhibitors, epacadostat/pembrolizumab? I thought that looked awfully encouraging.

Reinhard Dummer, MD: Yes, I was really impressed by these data, and from both sides. First, from the efficacy and second, by the tolerability. This seems to be a promising approach, and you have to keep in mind that the monotherapy with the IDO1 inhibitor is more or less without any clinical benefit. There is really the hope that, together with the anti-PD-1 strategy, this will be promising. Well, it was quite a step to jump directly from the phase I into the phase III clinical trial. But, on the other hand, without a phase III clinical trial, we will never know. So, if you investigate this with these data, you have to do so in the right way, which is phase III. Additional phase II, I think, would not happen.

Jeffrey Weber, MD, PhD: It almost makes you want to have an early look, meaning, have a phase III design, and those designs exist where you can have an early look, almost like a randomized phase II trial. And then, if it looks good enough, you jump on to the big phase III, but you can include the earlier data within the total analysis.

Caroline Robert, MD, PhD: Exactly.

Axel Hauschild, MD: But the phase III is already activated; the trial is running already. They’re actively recruiting.

Dirk Schadendorf, MD: And recruiting like crazy.

Jeffrey Weber, MD, PhD: Yes, that’s the problem. If it recruits quickly, you can’t do that.

Axel Hauschild, MD: I was surprised when Reinhard was telling us about his biomarker panel in Zurich. Because he was including IDO1, already, as one of the biomarkers. IDO1, to my best knowledge, is a prognostic marker for melanoma. In fact, it is prognostic. But is it a prognostic and predictive marker?

Reinhard Dummer, MD: We don’t know, but we have it in our immunohistochemistry panel and we see stainings; the stainings work very nicely. We have some questions with the interpretation because the stains that stain mostly are endothelial cells.

Jeffrey Weber, MD, PhD: We’re getting close to the end. This has been incredibly informative. But before we end this outstanding discussion with 4 great colleagues, I’d like to get final thoughts from each of the panelists. So, Reinhard, Dr. Dummer, what’s your final thought to wrap things up?

Reinhard Dummer, MD: We live in exciting times! We are privileged that we are in this. And we have a lot to do. I think this is a great opportunity for academia to create developments that will help our patients.

Jeffrey Weber, MD, PhD: Axel, Dr. Hauschild?

Axel Hauschild, MD: Just like the other panelists, I have been in the field for more than 20 years and I had numerous clinical trials that failed to demonstrate even a response rate difference. So, it’s fantastic to see all these clinical trials coming up and 8 new drugs approved in just 5 years. I believe the future lies in combinational and sequential approaches, which are intelligent, and only biomarker studies can help us to distinguish the best schedule from a schedule that is likely to be as efficacious.

Jeffrey Weber, MD, PhD: Caroline, Dr. Robert?

Caroline Robert, MD, PhD: Yes, I agree. And I think the ground is moving under our feet. We have new drugs, new toxicity to manage, new classification for the RECIST, and new classification for the melanoma is going to arrive. So, we have to do frequent dates like that. And it was not Peer Exchange®, it was Legend of the Fall think.

Jeffrey Weber, MD, PhD: Okay. And Dirk, Dr. Schadendorf?

Dirk Schadendorf, MD: So, I think we have come, over the last 5 or 6 years, from a graveyard to close to heaven now. I think this is a transformation, which is unmatched and unseen. I was afraid that, after all the successful trials and drugs now available, that there would not be enough interest to keep the science and the development going. And I’m pleased to see that so many more companies and drugs and drug combinations are being tested now in the field of melanoma, actually paving the way for targeted therapy as well as for our checkpoint blockade in other fields of oncology. This is very gratifying.

Jeffrey Weber, MD, PhD: Great. So, thanks to all of you for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this Peer Exchange® discussion to be useful and informative. Thank you very much.

Transcript Edited for Clarity
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