No LP at ImVac yesterday, it was Bosch. We talked for a short while and I listened to his presentation. Much different than anything LP gives, as this audience of about 25 peer scientists were very technical and advanced. It was only about 25 minutes long, and the first half was methodology of proving that the immune response was present. Basically done by detecting immune responses like TNF, IL-6 and IL-8 within the injected tumors and clear activation of CD4 and CD8 with evidence from staining.
The second half was dedicated to case studies from the direct trial, most of which we already know and none with biopsy reports from week 16 yet. Very quick summation of the 4 case studies:
1 - Melanoma, wk 8 biopsy. Granulomas and T-cell infiltration at the site, no tumor cells detected in the lesion or the lymph nodes (lymph nodes, however, were not checked pre-treatment)
2 - mCRC (metastatic Colorectal), wk 8. Granulomas, no tumor cells detected in biopsy. Tumor has increased in size, but patient boasted of how great he was feeling and wouldn't think of discontinuing treatment. He/she is nearing wk-16 injection
3 - mCRC, day 7. Extremely active T-cells. May have had CD8 cells already present, must look at prior treatment. All of these patients have had multiple treatments in wide varieties.
4 - Sarcoma, wk 16. Moderate immune response, large necrosis. T-cell receptor sequencing revealed significant increase in T-cells from day 7 to week 8, 16 (wk 8 and 16 were close to even amounts). This suggests a systemic response. I believe this is new information.
There wasn't enough time to discuss everything the regulars here ask about, but we touched on a few things. For example...
The main reason for the changes to the trial were based on findings in the scientific community on MGMT Methylation and the depression of WBC in a large portion of the trial. Since the PFS and OS in that group are predictably lower, the design has to also see them as a subgroup. I personally think this means the total events has to increase in order to reach enough events for statistical relevancy in the non-depressed group. If it is known with high certainty that this group exists, it will be too late to account for it after the results are in. If they did in fact drag the numbers down, and the FDA could ask for another trial to prove it. Best to account for it now.
The new interim analyses for the trial are at 60% and 80% as usual (149 and 198 events). I suspect that if the subgroup was only slightly affected to the point where their PFS and OS are still improved >6 months, the overall group results at 149 events will be powered enough for efficacy halt.
Enrollment estimates and trial length are based somewhat on the European sites all becoming active. They are higher volume hospitals (on average) and enroll at much faster rates than most of the US sites. Hoping for new trial sites soon.
Wish I could stick around and blog about it all day, but gotta work. BTW - Marnix Bosch, really like that guy.
