Replies to post #222111 on Biotech Values

[JohnWayne]

Here’s link to interim 067 manuscript: https://www.nejm.org/doi/full/10.1056/NEJMoa1504030

sorry for double post, on mobile and not sure how to edit.

[jq1234]

>> Are the data so good that it looks clearly better than what you could expect from Opdivo monotherapy in a small study at (I’m assuming) top US academic centers? I don’t think so.


Exactly. People shouldn’t compare n=38 with ph3 with n>300. Look at epacadostat combination with pembrolizumab or nivolumab, similar or even better ORR/CR compared to NKTR-214/nivolumab in small trials. Once they expand into large ph3 when they enrolled more diverse and sicker patients, epacadostat + pembrolizumab ORR plummeted: ORR from 58% to 34%, CR from 26% to 4% while pembrolizumab relatively consistent with previous ph3. So, one needs to discount small n study significantly from ph3 trial. I don’t think this would settle until ph3 confirm one way or the other. I would’ve given NKTR-214 more benefit of doubt if monotherapy had produced ORR like ipilimumab monotherapy did.

[jq1234]

>> Opdivo monotherapy ORR in PD-L1 “negative” was 41%, granted using a 5% cutoff.

In the same trial PD-L1 < 1% only:

Nivolumab monotherapy ORR=35%, nivolumab/ipilimumab ORR=54%, ipilimumab ORR=18%.

As I said before, melanoma and RCC are not right indications to test PD-L1- conversion to PD-L1+ theory based on small n single arm trial because PD1/PD-L1 are doing quite well as monotherapy in this population.

[DewDiligence]

...the interim report of CheckMate-067 had 8.9% CR rate for Opdivo monotherapy. Opdivo + Yervoy CR rate was 11.5%.

I re-listened to the NKTR webcast Q&A (starting at time point 1:02:00), and confirmed that NKTR's CMO refers to the 2015 interim (PFS) analysis of CHECKPOINT-067, and the CR rates she uses for comparison purposes are as you stated (above). Thanks for weighing in.