Wino115 wrote: Yep - and 1b is a step in that direction but given it's "basket", there is no one cancer where the number will be statistically significant unless you had some crazy situatino where the step-up to 25 patients in one trial sees something like >50% ORR. But we should be able to draw some conclusions around de-risking certain elements so it moves the program up in value possibly. As I've often stated, the Phase 1 into 2 if successful is the biggest % ROI as shareholder. It's usually around 5x, with all the caveats around starting point (THTX is exceptionally low market cap relative to commercial opportunity if there's good news), market environment (lousy now), etc...
That's just how trials are logically designed.
First step -- find the tolerable level of dosage based on safety signals you learn.
Second step -- take that dosage and use a very small group to get a more robust data set to analyze for both safety, tolerability and pharmacological/efficacy by patient type, cancer type, etc..
This first phase is really all about safety, tolerability, dosage, recording the actions you see (hopefully strong enough to keep going to Phase 2). So in these steps --where we are now --nothing will really be "statistically significant" in the mathematical sense in all likelihood because it's designed to be a mini trial.
Phase 2 - Use your safety, dosage and efficacy data to design a trial that will be a "mini-pivotal" because it really focuses much more on the efficacy question. Safety is still in the equation, but this is where you want a statistically significant reading on efficacy so Phase 3 (which will be even larger) is worth your investment. By this stage, you should have de-risked a large majority of the key conceptual issues even without statistical significance if you miss the p-values needed because of size. You may get it, but shoudn't expect it.
Phase 3. Bigger yet, same issues, but since you are aiming for commercailization you include a much deeper dive in to issues like effectiveness, how it compares to SOC out there, and the risk/benefit issues for doctors to understand it's possible usage. This puts the commercial picture really in to view for doctors and patients.
Phase 4 - LT safety/effectiveness.
smallcapinv wrote: "These 1a patients were only there for a dosage study, not optimized for efficacy or a large enough sample to say anything."-Wino115
Time will tell when sample size is meanigful and when sort expression is known in each patient. That is my take - take it or leave it