Mfglola--as far as the rollover protocol may work

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Mfglola--as far as the rollover protocol may work out--how do they define "disease progression" in solid tumor trials? I'm thinking it would be visual measurement revealing tumor growth, but do they define it as, say 25% larger, or something like that?

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I believe greater than a 20% increase in tumor size is deemed progression.

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If leronlimab upregulates PD-L1 in a 90-day timeframe, would you see disease progression--or on the other hand, regression of the tumor--in such a short timeframe? Progression or regression in 90 days?

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Being a layperson, I could not even offer to speculate. But if the tumor shrunk 30%, the patient would be considered a responder. Subsequently, if the tumor grew 20% (tumor still smaller than original tumor size) the patient would be considered to have progressed. I believe this patient would then be rolled over to receive ICI provided they had elevated PD-L1.

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If the protocol is changed to give people an ICI as soon as their PD-L1 numbers rise we are not going to get much in the way of ORR numbers, or other information regarding leronlimab's effect on metastasis or survival as a mono-therapy. That means we will probably fail the original endpoint of the trial--ORR. (Fail the trial but save lives... that would be a Cytodyn-like thing to do, wouldn't it?).

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We would have ORR results based on the leronlimab + ICI combination but not leronlimab mono therapy. If FDA is going to approve a drug, my guess is they want to see that leronlimab alone provides benefit.

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Changing endpoints after the trial started, introducing a new drug into the mix, with limited data on the combos... I get the feeling the FDA does not like to do that kind of thing.

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This may mean the rollover protocol is the best way to go. Give FDA what they want is likely the quickest way to approval.

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But any deaths would be on the FDA.

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Maybe. From our mTNBC results, "7 patients were treated with leronlimab in combination with atezolizumab (n=4), or subsequently with pembrolizumab (n=2) or nivolumab (n=1)." Those treated "subsequently" with ICI had stopped receiving leronlimab. Was that due to Cytodyn terminating the trial and stopping treatment or had the patients already progressed on leronlimab? How many of the 5 survivors had progressed on leronlimab before receiving ICI? Answers to those questions could make the rollover protocol reasonable in the opinion of FDA....