RE:Cancer phase 1 expectations There is an efficacy hypothesis they are testing here. The reason these patients have no options is in part because their cancer has become resistant to drugs. The hypothesis is that th1902 bypasses some of the resistance mechanisms by delivering the drug into the cell in a new way. So if the drug is going to work it should work on some of these optionless patients. I think therefore you can be a little more positive than you're being here but there are some caveats.
In Ph1 part 1 they are taking "all-comers", that is all solid tumours (not just the ones tested preclinically) and they aren't screening for sortilin. So potentially they are going to be enrolling some patients with no sortilin, in which case the drug is unlikely to work or cancers which for others reasons it is ineffective. As you say the main focus in this part is safety, pk/Pd, MTD etc so it doesn't really matter (from the trial perspective) if these patients respond, efficacy is secondary. I would hope though that in the hotchpotch of patients they are picking up for part 1 that at least one or two show shrinking tumours,it doesn't have to be many but some sort of Proof of Concept signal is possible, as you say though we could feasibly get thru part 1 without seeing that.
Ultimately though the drug can't just have anti-tumour properties it also needs to have some utility in the clinic, it has to be leading to enough patient responses for it to be worthwhile for doctors to reach for it and those responses need to be deep and/or durable. I wouldn't be trying to think about hints of ORR or other measures like that until they get deep into part 2 of Ph1 and the expansion into Ph2 (if that happens) but if we are looking for a drug with utility I'd want to start reading about shrinking tumours as soon as possible.
I think on the efficacy side I'm thinking about a PoC signal from the Ph1. How robust that signal is will be a pointer to later ORR and the drugs competitiveness. You can see with ADCs used in these hard to treat patients an efficacy signal in the first couple of dozen patients once the drug reaches it efficacious dose, we need to see something to match that. THTX are taking a slightly different route to others in that they are leading with a basket trial, that has some implications for how the data needs to be interpreted, it might push back shedding light on ORR while they sort out effective from ineffective indications.
I'd agree with you though if there is no efficacy signal in part 1 it's not a failure.
jeffm34 wrote: I think we have to temper expectations of efficacy in the phase 1 trial. They are enrolling patients with no other options left so their prognosis is very poor. Success in this trial will be if TH1902 is no more toxic than docetaxel alone. If there are no significant signs of efficacy, it is not necessarily a failure. If there is significant efficacy in this patient population it would be pretty amazing to say the least.
The phase 1 study will comprise dose-escalation and dose-expansion portions.7 Patients have to have recurrent advanced solid tumors, have relapsed on or be refractory to standard chemotherapy, surgery, and radiation, and have no effective alternative treatment options to be eligible for the first-in-human study of TH1902.