Response Rate is a measure of anti-cancer drug activity. It's more reliable in early phase trials than PFS estimates ... yet to be analyzed with great scrutiny!
Thanks for the excellent post! In your opinion, what would be the most reliable endpoint (or composite endpoint) to access early signals of activity in a phase 1/1b trial?
Thoughtful (publicly available) reflections on the reasons for P2 "pos" resulting in P3 "neg" trials are in short supply as the companies 'have to' downplay all the real reasons why ORRs, DoRs and everything else drop like a rock between P2-AAs and subsequent P3 trial.
I'd like to add that, in my opinion, P1-2 -> P3 trials with novel drug candidates as a general rule of thumb should NOT have the same efficacy numbers within the trial cascade.
For a dummy clinician like me, to conduct ethically valid human trials with novel cancer drugs that have potential/unknown benefits and harms, the patients recruited for P1-2 trials should have the utmost highest probability of receiving more benefits than harms from the novel drug. And it takes more than handful P1 trial participants with a given dosage to denote the frequency and severity of AEs to acceptable level of uncertainty. Then, IF researchers understand the novel drug and the disease they study, P1-P2-P3 trial cascade should NOT exhibit common efficacy readings in terms of RRs, PFS, OS, AEs and such. If promising enough P1-2 data, then P3 trial should focus on larger patient population that is less cherry picked.
On the other hand, a drug that is looking out for 10th indication should conduct more generalizable P2 trials to save the time and money of every stakeholder out there, right?
This is an uninformed and overly negative "hot take".
It's dose escalation so nobody cares about about doses < RP2D(s) (160 - 300 mg) for efficacy evaluation. Yes they matter for safety but that's not the topic at hand.
N=97 includes early d/c (e.g., PD or TEAE d/c leading to no post-baseline scan); note verbiage "potential scans" meant to address this.
However, agree they should take out uPRs and present ORR as a range. uPRs that are ongoing should not be automatically assumed to be PD.
Waterfall shows 3 uPRs still on tx --> N=17 to 20 responses @ RP2Ds gives a cORR range of 18% - 21% for RASm ORR14+ group.
Thanks for the excellent post! In your opinion, what would be the most reliable endpoint (or composite endpoint) to access early signals of activity in a phase 1/1b trial?
For a drug with expected single agent activity, that is.
Thoughtful (publicly available) reflections on the reasons for P2 "pos" resulting in P3 "neg" trials are in short supply as the companies 'have to' downplay all the real reasons why ORRs, DoRs and everything else drop like a rock between P2-AAs and subsequent P3 trial.
I'd like to add that, in my opinion, P1-2 -> P3 trials with novel drug candidates as a general rule of thumb should NOT have the same efficacy numbers within the trial cascade.
For a dummy clinician like me, to conduct ethically valid human trials with novel cancer drugs that have potential/unknown benefits and harms, the patients recruited for P1-2 trials should have the utmost highest probability of receiving more benefits than harms from the novel drug. And it takes more than handful P1 trial participants with a given dosage to denote the frequency and severity of AEs to acceptable level of uncertainty. Then, IF researchers understand the novel drug and the disease they study, P1-P2-P3 trial cascade should NOT exhibit common efficacy readings in terms of RRs, PFS, OS, AEs and such. If promising enough P1-2 data, then P3 trial should focus on larger patient population that is less cherry picked.
On the other hand, a drug that is looking out for 10th indication should conduct more generalizable P2 trials to save the time and money of every stakeholder out there, right?
This is an uninformed and overly negative "hot take".
It's dose escalation so nobody cares about about doses < RP2D(s) (160 - 300 mg) for efficacy evaluation. Yes they matter for safety but that's not the topic at hand.
N=97 includes early d/c (e.g., PD or TEAE d/c leading to no post-baseline scan); note verbiage "potential scans" meant to address this.
However, agree they should take out uPRs and present ORR as a range. uPRs that are ongoing should not be automatically assumed to be PD.
Waterfall shows 3 uPRs still on tx --> N=17 to 20 responses @ RP2Ds gives a cORR range of 18% - 21% for RASm ORR14+ group.