READ! PHASE 3 MSS-CRC Immunotherapy Trial Just Registered!! (Cobi + Atezo)

[DK37]

BIG MSS-CRC TRIAL NEWS

A VERY IMPORTANT new Phase 3 immunotherapy trial has been registered to start soon for CRC – details below.

Print out the links to have an informed discussion with your MD(s) to determine if it would be a good part of your treatment plan.
Full data is being released in an oral presentation at ASCO on Sunday, hopefully a publication will arrive soon.

NCT02788279: https://clinicaltrials.gov/ct2/show/NCT ... 279&rank=1

Based upon the Cobimetinib (MEK inhibitor) + Atezolizumab (PDL1 inhibitor immunotherapy) Phase 1 trial whose full results are coming out at ASCO on Sunday http://abstracts.asco.org/176/AbstView_176_171295.html

Preclinical rationale: http://www.cell.com/immunity/abstract/S1074-7613(16)30011-5

Presumably based upon their belief in the strength of the Phase 1 data – the developing company is SKIPPING PHASE 2 and going directly into a randomized PHASE 3 trial set up for accelerated FDA approval – IF PHASE 3 DATA SUPPORTS.

Phase 3 trial details:
- 360 patients across 42 locations
- 3-arm randomized study (1/3 chance of getting each arm by luck of draw). Arm 1: Patients will get Atexolizumab (PDL1 inhibitor alone). Arm 2: Patients will get Cobimetinib + Atezolizumab Arm 3: Patients will get current standard of care Regorafenib as comparator
- ENROLLMENT MIMICKING NATURAL STAGE IV CRC PATIENT POPULATION (50% KRAS-wildtype, rest KRAS-mutant; 5% MSI-high, rest MSS) – implies that they are attempting to get a very general FDA approval for “Stage IV CRC”.
- Relatively lenient in terms of past chemotherapy. Need to have either failed or been “intolerant to” two lines of chemo prior to trial.
- Can NOT have taken previously any of these: 1.) ANY immunotherapy 2.) Any MEK inhibitor 3.) Regorafenib
- Can not have had a second cancer within 3 years
- Can not have a history autoimmune disease
- Additional exclusions apply (listed in the NCT link above)

Overall – there are some aspects which are not ideal for a current patients (e.g. some of the exclusion criteria, randomization) – but this is an ideal set up for fast FDA approval to bring an immunotherapy to the MSS-CRC masses ASAP (IF PHASE 3 DATA SUPPORTS!)

I’ve been pounding my fist for a long time that I strongly believed combination therapy tricks would work in MSS-CRC. This is the next BIG STEP FORWARD to prove that belief clinically!

Same combination I blogged about last week: https://adventuresinlivingterminallyopt ... al-cancer/

A very good day for MSS-CRC that the developing company feels strongly enough about their Phase 1 data to “go for” an accelerated approval.

Crossing fingers now that the Phase 3 data turns out well…

Cheers! -DK

[Stanfordmom]

Thank you for posting this, Tom!

my oncologist at Stanford also said that this is coming but is a blinded study.

Looking at the timeline, it looks like probably still three more years for FDA approval, ha?

Sha

[juliej]

I can't wait to hear the full data results on Sunday! They must be pretty phenomenal to go straight to a Phase 3 trial. I'm not happy with the randomized part, but I understand it's necessary for some trials. Also, the first trial is still recruiting (except in the Tennessee location), so if a patient doesn't want to take a chance on randomizing, they can try for it.

The main thing is we have our first strong contender for taking on MSS CRC!

Looking at the timeline, it looks like probably still three more years for FDA approval, ha?

Sha, I know this is shorter than the old 7-10 year standard, but in my opinion it is simply too long! The FDA needs to do something different in the way of endpoints for immunotherapy trials. They need to see how long patients live after taking the trial drugs, not simply look for results in CT scans at empiric points in time. Faster Cures is working to speed up the process, but we need to expand patient engagement, increase collaboration between research teams, and enhance the FDA's capacity and resources before we'll see a real change.

[DK37]

I don't have a crystal ball but I am hopeful (if the medicines work as hoped) that it will be less than 3 years. The FDA is being very efficient when it comes to immunotherapy data analysis - much more so than historically with traditional drugs. They know they are game changers.

Based upon other cancer types:
- IF the data looks good, they will open up access expanded access prior to FDA approval while final paperwork is being assembled.
- For one of the lung cancer trials, the FDA came back with a decision in 4 DAYS after the final application was submitted because they had been reviewing the data on a rolling basis during the trial process.
- Other companies have MEK inhibitors and PD(L)1 inhibitors - assuming the data on Sunday is good (which it should be since Genentech/Roche is going directly into Phase 3!) expect other companies to be jumping in too with competing trials - opening up more trial slots and locations for patients.

-DK

[Steph20021]

I am so happy to read this tonight! And to see that three cities in Ontario will be recruiting, including Toronto.

I am curious, and this question applies for all trials and it may be a silly question but if you end up in an arm of a trial that isn't working for you (as shown by tumour spread or growth), do you get to then switch over to a different arm of the trial? Or no, are you out of the trial altogether?

[DK37]

I am so happy to read this tonight! And to see that three cities in Ontario will be recruiting, including Toronto.

I am curious, and this question applies for all trials and it may be a silly question but if you end up in an arm of a trial that isn't working for you (as shown by tumour spread or growth), do you get to then switch over to a different arm of the trial? Or no, are you out of the trial altogether?

A good question. Rules depend on the trial but most commonly, you would not be able to switch over to a different trial arm due to progression, you would be out of the trial. If there is a really big difference in efficacy seen while the trial is in progress, for ethical reasons, they may end the trial early, shut down the poorly performing arm and move all patients to the active arm.

Moving directly from Phase 1 to Phase 3 is great news for the overall patient population because it will dramatically speed up potential FDA approval timelines to make the combination widely available (IF the Phase 3 data is good!). But moving directly to Phase 3 isn't ideal from a trial participant point of view because unlike Phase 2 - participants are not guaranteed getting the experimental combination immunotherapy...

-DK