The First Phase 3 Checkpoint Immunotherapy Trial for MSS Colorectal Cancer
I usually only do this kind of “real-time trial news” post on my Facebook or Twitter accounts but this is such BIG news, I wanted to publish here as well to spread the word to the colorectal cancer (CRC) patient & caregiver portion of my Blog readership.
A PHASE 3 Immunotherapy Clinical Trial was registered today – including for MSS-CRC, the major type of CRC (95% of Stage IV) and the type I have! This is the first time ever that a checkpoint immunotherapy Phase 3 clinical trial has been announced for MSS-CRC!
This is the same immunotherapy combination (MEK inhibitor + PDL1 inhibitor) that I blogged about last week in my post: ASCO 2016 PREVIEW: CHECKPOINT IMMUNOTHERAPY ACTIVITY IN MSS COLORECTAL CANCER
Full data from the Phase 1 trial will be presented on Sunday June 5 at the ASCO annual meeting and I will update my blog once that data is released! There are a number of things suggesting that the data will be very good though: The developing company is skipping over a Phase 2 trial and going directly to a randomized Phase 3 trial shooting for the fastest potential path for FDA approval (if Phase 3 data supports this!).
Today’s announcement was a surprise – at least to me – it is abnormal and bold… As I wrote in last week’s blog post; “This was not a low risk study to run – it was bold. But as I have said before, big problems like MSS-CRC immunotherapy need bold solutions!”
I am waiting with baited breath for the full data on Sunday. Like AACR-2016 (which I also could not go to), I know a lot of people going to ASCO who will be relaying data back to me ASAP!
Regardless of the data specifics, what is even more clear now with today’s Phase 3 trial announcement than when I wrote last week’s post – a major step scientific step forward has indeed occurred in the immunotherapy treatment of MSS-CRC, otherwise the Phase 2 trial would not be skipped……… Data specifics aside, this is something to scientifically cheer for!
Of particular note: They designed the Phase 3 trial enrollment to mimic the natural Stage IV CRC Patient Population (50% KRAS-wildtype, rest KRAS-mutant; 5% MSI-high, rest MSS) – which implies that they are attempting to get a very general FDA approval for “Stage IV CRC”. This is very interesting since MEK inhibitors have traditionally been used to target KRAS-mutant cancers – but the preclinical paper linked below established the possibility of an immune cell targeted effect which could be independent of tumor genetics. I will be especially listening for KRAS-wildtype data in Sunday’s presentation since it was not included in the written abstract.
Here is the nuts & bolts summary for the trial (edited form of my Facebook post) – mostly of interest to fellow patients and their caregivers:
BIG MSS-CRC TRIAL NEWS – SHARE!
A VERY IMPORTANT new Phase 3 immunotherapy trial has been registered to start soon for CRC – details below.
Consider printing out the links to have an informed discussion with your MD(s) to determine with him/her/them if this trial would be an appropriate part of your treatment plan.
Full data is being released in an oral presentation at ASCO on Sunday (will be added to this blog then), hopefully a publication will arrive soon thereafter. Of note: I am hoping they will release data on KRAS-wildtype patients on Sunday since this was missing from the abstract.
Trial = NCT02788279: https://clinicaltrials.gov/ct2/show/NCT02788279?term=NCT02788279&rank=1
It is 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 for this combination: 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 the possibility of 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 Atezolizumab (PDL1 inhibitor alone). Arm 2: Patients will get the Cobimetinib (MEK inhibitor)+ Atezolizumab (PDL1 inhibitor) combination Arm 3: Patients will get the current standard of care drug 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/labeling 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 of autoimmune disease
– Additional exclusions apply (listed in the NCT link above)
Of note: Some patients mistakenly equate immunotherapy drugs as having no toxicity or side effects. This is not the case – these are powerful drugs interacting with the immune system and in some patients, significant side effects can occur. Until a larger number of patients are tested, this experimental combo’s full safety & toxicity profile will not be known.
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 trial set up for a potential 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 checkpoint inhibitor combination therapy tricks would work soon in MSS-CRC. This is the next BIG SCIENTIFIC STEP FORWARD to hopefully prove that belief clinically!
Next update will be on Sunday. Then it will be crossing fingers that the Phase 3 data turns out well…