New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

[DK37]

Hi Everyone,

I’m not sure if these have been mentioned before. I noticed 2 new recently opened PD-1 inhibitor immunotherapy combination clinical trials that either accept all types of CRC or are specifically intended for MSS-CRC (note I said MSS!).

As I have mentioned before, scientists hope that PD-1/PD-L1 inhibitors can become a backbone therapy for many cancers (including CRC) in the future with additional drugs added to them as a combination cocktail, to hopefully make them active against MSS-CRC (and also to hopefully improve response rate and/or durability of response in MSI-CRC).

Also, I wanted to note that as a strategic choice, many combination trials with PD-1/PD-L1 inhibitors EXCLUDE patients who have previously taken them – so choosing to sign up for a PD-1/PD-L1 inhibitor trial should “strategically” not be taken lightly – you might be precluded from some future PD-1/PD-L1 combination trials if future trials are needed. These trials are all highly experimental, since the “tricks” needed to get PD-1/PD-L1 activity in MSS-CRC have not been proven yet in clinical trials, although there are indications various combination therapies could work based upon pre-clinical animal models.

Here are the 2 trials:

1.) NCT02512172. New Phase 1. Johns Hopkins. Combination of: Two epigenetic modifying drugs + anti-PD1 MK-3475 (pembrolizumab). Intended to try to make MSS-CRC tumors more easily seen by the immune system. https://clinicaltrials.gov/ct2/show/NCT ... 15&rank=14
2.) NCT02526017. New Phase 1. So far in San Antonio, they want to accrue hundreds of patients so I believe will be expanding to multiple sites. Combination of anti-CSF1R antibody + anti-PD1 Nivolumab. Intended to try to make CRC tumors less immunosuppressive. https://clinicaltrials.gov/ct2/show/NCT ... 15&rank=40

Cheers,
-DK

[Carolinagirl]

This information is so incredibly helpful! Thank you!!

[JFrog]

Thank you so much, great info. Our docs at MDA have said there are more combo immunotherapy trials opening very soon for MSS.

[gator.girl]

Thanks DK! This is exciting for MSS! So stressful though to have to play this strategically.... Yikes - when do you know to jump in?

Rachel

[jortego128]

Thanks for the update Tom! These trials cant come fast enough!

[DK37]

Thanks DK! This is exciting for MSS! So stressful though to have to play this strategically.... Yikes - when do you know to jump in?

Rachel

That's the gazillion dollar strategy question Rachel... I wish I had a good answer... Because of potential later trial exclusion, personally I would be a little nervous doing a PD-1 trial until either 1.) There was word filtering e.g. here on Colon Talk that results were good from a particular combination or 2.) I was starting to run out of other options. BUT - I fully and openly say that this is just my personal opinion - there is certainly no right or wrong strategic answers, we're all (including me!) just guessing what path to follow without actual data in hand... The original & current MSI-CRC folks on the PD-1 trial bravely took a big risk (even with the above strategic consequences) and many of them have seen a response! Now it is MSS-CRC's turn to find our active immunotherapy...

-DK

[ieowi]

DK37,

I cant thank you enough for sharing all these information and updates ! thank youuuuuuu I always look to read your posts here.