anti-PDL 1, anti-PD 1 - 1259996

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ssflxl
anti-PDL 1, anti-PD 1 - 1259996

Dear All,

I just found out that the Phase II trial for MPDL3280A is now closed due to its popularity. I have heard rumblings that this agent doesn't work well for EGFR mutant patients, especially those who become resistant. I would like to know if anyone else heard that. If that is the case, then I would not push so hard to get into the Phase I trial for MK3475 at UCSF.

thanks

ssflxl

Dr West
Reply To: anti-PDL 1, anti-PD 1

I haven't heard that -- haven't heard anything either way about response rates in patients with EGFR mutations and imagine we're probably talking about quite small numbers, likely anecdotal experience. Considering that we're talking about an agent/class of agents with a response rate of 20-25%, potentially having a collective experience of very few responders among perhaps one or at most a couple of dozen patients with an EGFR mutation seems like a very small sample from which to draw broad conclusions.

It may well be true, as further evaluation may tell, but I think most lung cancer specialists are wary about interpreting too much too early.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

carrigallen
Reply To: anti-PDL 1, anti-PD 1

There is a hint of data emerging that smoking history seems to correlate with higher response rate to this class of anti-PD-L1/PD1 drug. Nothing firm has been reported on this yet though, except for the upcoming World Lung Conference this month. There is currently an effort by researchers to look back to correlate response with factors like mutation status in available patients, although this is really just idea-forming research. The bottom line, as Dr West says, is that there isn't enough information yet to draw conclusions.

ssflxl
Reply To: anti-PDL 1, anti-PD 1

Dear Drs.

Thanks for your perspective. I suppose this stuff works well if it does work.

ssflxl

Dr West
Reply To: anti-PDL 1, anti-PD 1

I should say that, as Dr. Creelan noted, I have also heard that we're going to be seeing data that people with a history of smoking have a greater probability of benefit with the immune checkpoint inhibitors. That should be an interesting angle for future development of these agents.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

catdander
Reply To: anti-PDL 1, anti-PD 1

abstracts for the conference are here, http://abstracts.webges.com/wclc2013/myitinerary

Jazz
Reply To: anti-PDL 1, anti-PD 1

How right you are, SSFLXL. Darn it. I even had a referral to that trial but I waited too long...Cohort 2 (previous treatment exposure) is closed. Oh well. On to MK-3475 I suppose. I've just been told late November - early December for Clovis trial. So in the meantime I guess I'll just let Merck/UCLA do the biopsy...

It works well if it works, but if you've got nothing else to try, it's probably as good a bet as Navelbine (in my case). How are you, SSFLXL?

Jazz

ssflxl
Reply To: anti-PDL 1, anti-PD 1

Jazz,

I found out that Stanford has another MPD trial, and it's Phase 1 - has not started recruiting yet, but it's for all solid tumors, so it doesn't sound like you need to have +PD 1 to qualify. you should look again at their website.
UCSF has the MK3476 Phase 1 trial and you would qualify, but not me because you have to fail chemo.
My tumor has grown and I have another small one. My onc thinks it's time to change treatment. Luckily, I don't have "much" symptom yet. I prefer to go on a trial first before chemo, but the anti PD trials in Stanford and UCSF both require Platinum failure. I hope to get on the Clovis trial at Stanford, but will need biopsy to show T790M. I have not had rebiopsy yet since I am not sure what trial I am going into or if I can get into. If I can't get into the Clovis trial, then I will start chemo. I hope I can wait until Jan - don't want to start anything new over the holidays unless I can't help it.

thanks for asking Jazz

ssflxl

Jazz
Reply To: anti-PDL 1, anti-PD 1

ssflxl,

Looking at the Stanford website, I'm surprised to hear the Phase 2 MPDL3280A trial is closed, as they just opened it and on clinicaltrials.gov it actually says "Not Yet Recruiting". The Phase 1 for solid tumors remains open EXCEPT to Lung, as that's what the Phase 2 trial is for (Lung only). However, at Angeles Clinic and others around the country that have had the trial open for awhile, Cohort 2 (previously treated) of the Phase 2 trial is closed.

I believe UCLA is opening the trial but I don't see it on their website. I was told in August it would open in "about 3 months". Meanwhile the plan is to enroll on Monday (4th) in the MK-3475 trial, get biopsy done there, if positive will go forward, if negative hopefully a CO-1686 slot will be available... At this point, I'd just like to avoid Cisplatin-Navelbine - didn't realize I'd need a port/central line and it's a 7-hour infusion (which really means 9 hours, from my experience)

Dr. Garon of UCLA presented the prelim data on MK3475 in lung cancer at the IASLC conference in Australia, so they're hot to enroll people. They think the data is solid - 25% RR in PDL-1 positive and some response in the negative patients. I don't favor the agent due to the pneumonitis side effect (not good for one-lungers like me), but I'm assured it's "only 4%". To me that's high but I'm told Merck pays for everything and I wouldn't even have to bother with a Kaiser referral. We'll see about that! I'll keep you posted.

You're lucky to have an almost full "arsenal" of options still available. I hope you can ride out the holidays as well. You're a trooper :) Don't wait too long though - stay healthy. Do you attend the Bonnie Addario Lung Cancer Living Room meetings?

Cheers,
Jazz

ssflxl
Reply To: anti-PDL 1, anti-PD 1

Jazz

I also looked at the clnicaltrials.gov website on the Stanford trial - it states not recruiting, but I don't know how updated the website is since the government shutdown for 2 wks!!! My onc emailed Heather Wakelee and the following was part of her reply:

Unfortunately the trial was VERY popular and we nearly immediately filled our slots and then enrollment to the entire trial was closed last week. We will have another trial opening in the next couple of months with the compound.

UCSF has Phase 1 MK 3475 trial also.
I hope the CO 1686 trial at Stanford opens soon.

Hopefully, some of the anti-PD 1 agents can be approved by FDA next year since there are so many trials that filled up so quickly. we should see results soon enough and hopefully, FDA will approve them expeditiously.
I know I have been lucky to have lasted 3 years on Tarceva and my tumor has been slow growing.
I hope you get into something soon. How are you feeling these days?

ssflxl