RE:RE:RE:RE:RE:10 questions from RBC January 8 RECIST is the standardized protocol/rules of cancer studies, it's mentioned on thtx's clinicaltrials page. The wiki entry is a great place to start but there are many good guides to understand RECIST. I think it's worth getting familiar with it and familiar with how other companies report it because there are right and wrong ways to report this data and any company that starts to stray from reporting the data in the standard way are maybe trying to hide something.
https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors
The four categories of response are.
- Complete response (CR): Disappearance of all target lesions
- Partial response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD
- Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
- Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Overall Response Rate (ORR) is the total % of CR+PR group. What is recorded is the best response hit at any particular time point. So if a patient had their tumours measured 4 times and it went over time SD, PR, CR,PD then that patient gets catorgorized CR because that is the best response they hit.
Duration of Response (DOR) is the (mean) time from when the patient had their maximal response to the point their cancer re-started progressing. This can take time because it relies on time to pass to get an result but you can get reading like % with response at 6 months or 12 months to give some indication of the depth of response. Again using Sutro as an example they are reporting a number of durable responses hitting 6 and 12 months in their population.
Overall Survival is what it suggests, the time from initiation on trial to death. Obviously this might take a long time if people stay alive but they can report this in different ways so they might say % survival at 6 or12 months for example.
So if you read the literature one concern with chemo (and now also with ADCs) is in late line setting they don't give extended disease control so patients may respond but then relapse quickly. We have to watch for that with our PDC. Immunotherapeutics tend to give reverse outcomes, they often work in a limited number of patients but when they do they often give much longer benefits.
Clearly part of the reason to chase a PDC is to avoid toxicity. That paper was describe the present landscape of late treatment TNBC, toxicity of chemo is horrible, women have to come off drug early and this is contributing to the poor DOR. Fix toxicity and you might fix part of the DOR problem with chemo/ADCs. Again this is to some extent what Sutro have done, it allows some women to keep taking the drug for 1year+ and that helps maintain disease control. Let's start off by hoping for this from THTX's drug.
That paper I linked to just described how bad the drug landscape looks in the initial pop in TNBC that THTX is chasing. It just shows how low the bar is. I haven't looked deeply at all the indications THTX is chasing but they all look similarly dire.
SPCEO1 wrote: Since amny of us are not familiar with oncology, could yo give us a brief explanation of ORR, DOR and OS. Also, what is the toxicities issue?
I am also not sure what you meant when you were referring to the biopsy in NASH as a weakness. All NASH trials involve biopsies, so it is a weakness shared by all NASH companies.
qwerty22 wrote: I see cancer as data driven, it's hard to ignore ORR or DOR, they should speak loadly, I guess you could ignore them if you want to focus on corporate competence.
Here's a meta-analysis of mTNBC lots of numbers to pick out of that but my summary of the present tested drugs.
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1210-4#Tab1
10-20% ORR
4-6months DOR
12-18months OS
50-66% grade 3+ toxicities
This is what the drug needs to beat to look promising. Sutro is doing that but in Ovarian and the SP over the past 12-18 months looks great even with a drug related death.
I actually also see NASH as data driven and in that case very focused on the biopsy endpoints as the foundation for a program. I still think collectively we are under-estimating the importance of that weakness at least to the perception of the program.
scarlet1967 wrote: Most of questions are relevant but it seems there are so much pending doubts regarding company's ability to execute so even when they produce good results it won't be factored in by the market, I believe the problem is the failed IR and inability to convince the investors of course the recent deal wasn't helpful at all.
But if company can address these questions in a convincing manner going forward it will definitely help the valuation imo, therefore they need to have a serious discussions re changing their failed strategy.