Thanks for the link Twiz; it's nice to see that the UCSF biomarker study is garnering some attention considering they have identified a biomarker with 100% predictability for non-response in monotherapy anti-PD-1.
The metastatic melanoma patients enrolled in ONCS's investigator-sponsored (UCSF) phase II combination trial are selected - if my memory serves me correct - based on a less-than-25% PD-1/CTLA-4 TIL phenotype. What this means is that a patient has a 0% chance of responding with a <20% PD-1/CTLA-4-positive TIL phenotype and a 5% chance of responding with a 20%-25% PD-1/CTLA-4-positive TIL phenotype, if using pembrolizumab alone. Patients enrolled in the phase II combination trial would not - for all intents and purposes - theoretically respond if given pembrolizumab alone. Therefore, any responses in this phase II combination trial are quite significant.
Just a side note, the combination of Yervoy (anti-CTLA-4) and Opdivo (anti-PD-1) are one of the immunotherapy combinations nearly reaching 60% (59% ORR in metastatic melanoma) - see CheckMate-069. This suggests that the addition of an anti-CTLA-4 checkpoint inhibitor to an anti-PD-1 mAb is turning non-responders into responders - they are essentially doubling the response rates. The complete response rate was 22% - again, slightly more than double the rate with Opdivo used alone. I tend to think that combination EP IL-12 and pembrolizumab will observe slightly better ORR and complete responses based on IL-12's ability to drive an increase in "exhausted" phenotype TIL. In addition, 78% of advanced metastatic melanoma patients treated with combination Yervoy and Opdivo would be considered refractory, because they are either partial responders or non-responders. In other words, sustained 22% complete responses (remissions) observed in the Yervoy/Opdivo combination trial still leaves the door wide open to ONCS, because ONCS is going for the refractory population that is currently around 78% based on available information.
