for clarity's sake, why was the ICI Atezolizumabin chosen at all when it was shown to be ineffective otherwise? was it to prove it COULD be effective if a second drug like leronlimab was used to make the tumor "hot"? seems painfully risky to the patient even though patients were running out of options? cant imagine a doctor talking me into taking a drug the FDA already had deemed useless...? what am i missing here

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Our 5 survivors were treated with LL and an ICI. Of the 5 though, 4 were treated with Atezolizumabin, which showed little to no efficacy in their Phase 3 trial for mTNBC and led to the drug being discontinued by Roche before the FDA revoked their conditional approval. So, my question is, if Atezolizumabin was proven to be ineffective in mTNBC, did this ICI actually become effective because of LL or did this ICI do nothing like it did in its Phase 3 trial and it was all LL? If it's the latter, would that mean that the 5th patient who took Keytruda could have not benefitted from Keytruda at all and it was all LL.



In the initial atezolizumabin phase 3 trial that the FDA based their conditional approval on very good effect was shown in overall survival in PD-L1 positive patients. The follow-up trial showed terrible results. The definition of PD-L1 positive is defined as 1% or more expression. With such a low starting expression it may be a case of the first trial having a higher number of patients with a much higher expression of PD-L1 (hotter tumor) and the second trial having patients that were near 1% (colder tumor). PD-L1 inhibitors are going to do much better the hotter (more killer T-cells) there are. Without those killer T-cells the tumor will not be destroyed.

Leronlimab boosts those killer T-cells, the temporary (30-90 day) increase in PD-L1 when using leronlimab is just a side effect of that. The addition of PD-L1 inhibitors to leronlimab strips away that tumor defense mechanism allowing leronlimab to more effectively do its job.

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