Trial update - ATRIUM (ATG-018)

[Rock_Robster]

Hi all, just putting out there for anyone watching these things - I’m starting the ATRIUM clinical trial next week. It’s a phase 1 open label basket trial of an ATR inhibitor (ATR-018), targeting a range of mutations/biomarkers including in my case p53 (which is very common in colorectal cancers). Preclinical data is good (of course) and early human results are encouraging, but of course too early to say. I’ll be entering at 90% of target dose, and they haven’t had major issues with tolerability so far.

To be honest I see this as a bit of a ‘freebie’ trial and a break from chemo; given the vast majority of trials here are immunotherapy (about 90%), and you can generally only do one trial with PD-1 checkpoint inhibitor, figured I’d do this while waiting for the right immuno trial to open up (or back to chemo). And it’s a nice chemo break while hopefully doing something beneficial.

Shout out to enhanced biomarker testing for identifying my p53 mutation - well worth doing. Mine was done well (and free!) through the MoST clinical study.

Will update.
Rob

[prayingforccr]

Hoping for a robust response, rock robster

Congratulations on being proactive!

[beach sunrise]

This is good news!
Keep us in the loop.
p53 is a big one to knock down for sure.

[L0729]

I’m sure this is a stupid question: is p53 mutation the same as a tp53 mutation?

[Rock_Robster]

I’m sure this is a stupid question: is p53 mutation the same as a tp53 mutation?

Yep same thing, (tumor) protein 53.

[prayingforccr]

I’m sure this is a stupid question: is p53 mutation the same as a tp53 mutation?

Yep same thing, (tumor) protein 53.

One of my mutations, as well,:(

Almost all of my alternative treatments were geared to upregulating/turning it back on.

[Peregrine]

... I’.m starting the clinical trial next week. It’s a phase 1 open label basket trial of an ATR inhibitor (ATR-018), targeting a range of mutations/biomarkers including in my case p53 (which is very common in colorectal cancers). ...

A Study of ATG-018 (ATR Inhibitor) Treatment in Patients With Advanced Solid Tumors and Hematological Malignancies (ATRIUM)
https://classic.clinicaltrials.gov/ct2/show/NCT05338346

Detailed Description:
This is a Phase I, multi-center, open-label study of ATG-018 administered orally as monotherapy in patients with advanced solid tumors and hematological malignancies. The study design includes a Dose Escalation Phase and a Dose Expansion Phase.
...
After completion of Dose level 3, subjects will need to demonstrate a defect in one or more DDR genes such as: ATM (including ATM protein loss by IHC), ATRX, ARID1A, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, MSH2, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, or other related genes at the discretion of the investigator in consultation with sponsor Medical Monitor; Or mutations in p53 pathway/MYC pathway

Good luck on the trial !
I hope you have a strong response.

[beach sunrise]

R_R, were there any other heat shock proteins other than tp53?

[Rock_Robster]

R_R, were there any other heat shock proteins other than tp53?

I’m not an expert but I didn’t see any other HSPs on the qualifying list. Actually Peregrine’s post above has a good summary of the qualifying biomarkers/mutations.

[Rock_Robster]

R_R, were there any other heat shock proteins other than tp53?

Sorry, or did you mean in my personal disease biology?

[beach sunrise]

Sorry for the confusion, I confuse myself all the time!
I was wondering really if any other HSP's were found and whether or not they are considered mutations from p53?
In 2021 Signatera found tp53 with me but after recent lung surgery examination of tumors and blood no tp53 found but another one is showing up as a potential problem.
If this is still confusing tell me please.

[Peregrine]

R_R, were there any other heat shock proteins other than tp53?

For your information, here is a highly technical article that covers all types of stress proteins, including heat stress proteins (HSPs) as a special case. The section on HSPs is way over my head in terms of complexity, so I wouldn't be able to summarize it, but it does have a lot of detail about different kinds of HSPs and how they function.

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356129

[beach sunrise]

Thanks, Peregine! That is a brainful. I picked out a few things.
R_R, I am following you on this trial. I hope you have the best outcome!

[Rock_Robster]

Hi all, just to close this one out - my 6 week scans unfortunately showed the trial drug wasn’t working. Increase in size and number of liver metastases, and small increase in size of lung lesions. Won’t be continuing.

Next up, potential other trials, immuno, SIRT/Y90, and of course chemo options.

[rp1954]

Hi all, just to close this one out - my 6 week scans unfortunately showed the trial drug wasn’t working. Increase in size and number of liver metastases, and small increase in size of lung lesions. Won’t be continuing.

Of course that sucks, but on with the show.

I have two questions.
What was the physical cost of the Atrium trial in terms of side effects and blood panels?
What % of your work are you functioning at or willing to give up to work harder on yourself?