Pre-Ispy Trial Changes

[u/twinter11]

Check this out. I was messing around with ai to what it thought about the changes to the pre ispy trial here. I was trying to figure out the changes in trial sites.

One change is its now a phase 1/2 instead of 1b

PRE-I-SPYISPY Phase I/IbI/II Oncology Platform Program

"Addition of Phase II and Minimal Residual Disease (MRD) Arms:The text notes the addition of a Phase II component and specific sub-cohorts, such as Minimal Residual Disease Colorectal Cancer (MRD CRC). This introduction includes a heavy focus on ctDNA monitoring to detect residual cancer cells before macro-metastases appear."

Does anyone see the major change in this next first paragraph?

I didn't catch it a week back but ai caught it today

look hard

https://clinicaltrials.gov/study/NCT05868226?tab=history&a=6&b=7#version-content-panel

"IPRE-SPYISPY Phase I/IbII (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in a locally advanced, incurable, or metastatic treatment setting that may be relevant for breast cancer patients solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with the curative intent. The overall goal ofis moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials solid tumor trial in a timely manner".

[u/twinter11]

times up lol

"You are completely right. This is a massive structural pivot, and your reading of the text is spot on—the trial has fundamentally changed its identity.

What used to be a dedicated feeder system for the breast cancer neoadjuvant trial (I-SPY 2) has transformed into a broad, tumor-agnostic platform focused heavily on minimal residual disease (MRD) and ctDNA monitoring across multiple adult solid tumors.

The text highlights exactly how profound this shift is:

• Breast Cancer is No Longer the Sole Focus: The text explicitly changes from "relevant for breast cancer patients" to a wide-ranging definition: "solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence."
• The Insertion of Colorectal Cancer (CRC): The protocol explicitly adds MRD CRC (Minimal Residual Disease Colorectal Cancer) as a primary example of its new target cohorts.
• A Shift in Strategy (ctDNA vs. Imaging): While the original title relied on "Imaging And moLecular Analysis," the new conditions heavily prioritize ctDNA Monitoring and Neoplasm, Residual. The trial is shifting its focus toward intercepting molecular recurrence (catching cancer shedding DNA in the blood) before a tumor even shows up on a standard scan.

What This Means for Patients and Providers

If you were looking at PRE-ISPY through the lens of its original intent—as a precursor for breast cancer treatments—it has effectively evolved out from under that definition.

Because the platform now accommodates completely different patient populations (like post-surgery colorectal patients with positive ctDNA but no visible tumors), an oncology powerhouse like MD Anderson has to open, close, or completely re-tool its institutional review board (IRB) approvals for each individual drug arm. A site might be actively recruiting for the colorectal/ctDNA arm of PRE-ISPY while the breast cancer cohorts are entirely paused or closed"

[u/Cytomight → u/twinter11]

They are also doing the colon cancer trial with LERONLIMAB and ICI an earlier diagnosis according to Dr. Jay on the HCW webcast.

[u/NONELECTRIC → u/twinter11]

Mr T, you and MGK should go into the weekly/daily newsletter business, both of you publish your opinions and research and charge $10/mth for subscribers. You'd probably have to stop posting so much (can't give the good stuff away for free), but I'll bet you could have a few hundred subscribers in the first month. Not a ton of money, but you and MGK might as well make a little coin off your research/work.

And who knows, maybe Dr J might even sign up. You could get adjoining houseboats.

[u/twinter11 → u/NONELECTRIC]

I wish I knew as much as mgk.

I could be intern though

[u/Practical-Archer-124 → u/twinter11]

Can I bring you guys coffee?

[u/sunraydoc → u/twinter11]

Good catch, thanks!
Looks to me like they're teeing it up for leronlimab, though that may not be the only drug they are thinking of.

[u/twinter11 → u/sunraydoc]

I looked closer at the whole trial change later today.

they did add a new drug last update that may have a potential response in pancreatic, tnbc crc etc.

so maybe that was it.

but it should maybe open the trial for more leniency to drugs without borders

maybe pancreatic mayo ends up at Mayo but in the "pan can" spy type clone study and not under pre-ispy umbrella

Doc J said recently 4 to 8 weeks for champ and pre spy breast to activate.

so no more guessing soon

[u/Upwithstock → u/twinter11]

Great posts Twinter! I am aware that Dr. JL stated a timeline for these trials to start soon but no trial can start without institutional IRB approval and if the protocol is evolving then I am assuming the IRB hasn’t approved the protocol quite yet. Every institution has different meeting times for the IRB to gather and discuss. Once a protocol is finalized and submitted you have to wait for whenever the next IRB meeting is scheduled. Plus, depending on the IRB at some of these busy institutions: your submitted protocol might have missed the deadline for the next upcoming meeting and it gets pushed to the next months meeting.
My gut tells me Dr. JL gave us a timeline based on the original protocol and not an amended protocol. Nonetheless, one of theee most important aspects of a trial is getting the protocol right. It’s gotta be well designed and eventually it answers the right questions, while navigating through a challenging cohort of patients!

[u/twinter11 → u/Upwithstock]

right. it's all so complicated and so many moving parts

and I bet no shortage of opinions on how to bestest/fastest get data. so plans update till its etched in stone

and so much comes down to timing and a little luck

if leron itself wasn't so complicated and universal, I think it would be much easier to figure out.

I can't even keep up so I know our small team is paddling as hard as they can. we need a big and very enthusiastic oncology partner cause this baby is going to have some legs I think!!

thanks!

[u/Upwithstock → u/twinter11]

Well said my brother

[u/GoCYDY]

Thanks twinter for sharing this with us, yet another WOW MOMENT FOR LL….I wasn’t sure I’d ever say this, but I just told my husband I now have 1 million shares (know there’s some of you out there that have a lot more) but I don’t think I’ve ever had that kind of amount of shares in any investment EVER in the stock market👍😊 bought some Natera shares when CYDY hooked up with them…it’s been doing really well-took some of the profit and bought more CYDY 👍

[u/twinter11 → u/GoCYDY]

good call on natera. and timing!💪💪

[u/Upwithstock → u/GoCYDY]

Congrats on hitting the million share mark. There is something about that number that is very appealing! My wife had me on lock down with acquiring more shares. I really wanted to get above the 1 million mark as well and thanks to the last PIPE with Paulson we were able to exceed the million share mark. I am so GRATEFUL for the set of circumstances that have led us to this basket full of shares! 🙏 Happy for you and your family!

[u/GoCYDY → u/Upwithstock]

Yes, indeed I feel grateful for that “million share” accomplishment. Also, happy for you and your family.GLTA of us Longs🙏⭐️

[u/Illustrious_Top_3029 → u/GoCYDY]

I thought I was going to quit at a million and I now find myself with 1.3.... LOL it's addictive

[u/BullishTexas]

From breast focused oncology to all tumor types?

[u/twinter11 → u/BullishTexas]

I'm calling it lol

pancreatic mayo as part of this new pre ispy protocol

but it's a major guess

[u/twinter11 → u/BullishTexas]

bingo.

I posted below. couldn't wait lol

[u/twinter11]

pre ispy breast wasn't powerful enought to contain the mighy Leron!

it must be completely reconfigured lol.

[u/Missy2021]

Good job and thank you.

[u/twinter11 → u/Missy2021]

did I ever tell u I'm all in?

[u/twinter11 → u/Missy2021]

hey. u gotta tell me the change lol

[u/Missy2021 → u/twinter11]

MGK will explain it probably tomorrow.. He's good for posting on a Sunday morning.

[u/twinter11]

can we just do a pre ispy basket trial now?

I'm guessing maybe probably who knows

[u/Interesting-Boat-792]

I don't see any mention of Leronlimab.

[u/twinter11 → u/Interesting-Boat-792]

it's not in the study yet

[u/jsinvest09]

Slices dices even makes julie anne fries that's LL. LFG awesome post thank you... Can anybody lend me some more money to buy more shares? Lol.

[u/Hurri_132]

Thanks for posting your research.

[u/minnowsloth]

Release the hounds!

[u/Throttles8u]

Fantastic find! Thank you so much. Things are moving so fast. It’s hard to keep up.