ProstACT GLOBAL study. Will it turbocharge TLX591?

I thought I would start this thread to talk just about TLX 591 in the GLOBAL study post the SELECT study.

Check out the OS when in combination with Enzalutamide @flotsam222 (ENZA-p Study)

@mnbvcxz12345 cant wait for the data on this one

AndyHsieh

Oh, great.Thanks for taking our questions. A couple from us if you don't mind. So, one, Iwant to go back to the ProstACT GLOBAL study, especially with the dosimetryportion of the interim analysis. I'm curious if you will be able to detect whatDr. Louise Emmett had shown in the ENZA-p Study where enzalutamide couldupregulate PSMA expression. Just from that dose symmetry portion of your trial,as a way to kind of amplify the response? So that's question number one.

ChrisBehrenbruch

Yes. So Ithink it's kind of three questions there. The first one is verystraightforward. I mean, we obviously wouldn't estimate what we might see inclinical data that we haven't yet got in our hands. But you are right certainlythe – part of the basisfor the trial design is that there is a synergistic effect for both the RPs andin fact the taxanes, and up regulation of PSMA is one of them.

Thosepatients are scanned serially in the study. The dosimetry is a multi-time pointdosimetry study. So if there is an effect around PSMA expression levels, thenwe may well see it from the data. And that's exactly Richard commented and Iwon't ask him to repeat it, but that's why Richard commented having the comparative data between thethree different standard of cares is going to be really interesting. Andwe'll certainly put that commentary out there when it's available.

		Type	Pros	Cons
1	Enzalutamide	Androgen receptor inhibitor	- Oral tablet (easy to take) - No need for steroids - Effective in both mCRPC & mHSPC	- Fatigue, high blood pressure, falls, seizures (rare) - Cognitive side effects in older men
2	Abiraterone	CYP17 inhibitor (blocks androgen)	- Oral tablet - Effective in both mCRPC & mHSPC - Often well-tolerated	- Requires prednisone (steroid) - Liver toxicity - Fluid retention, high blood sugar
3	Docetaxel	Chemotherapy (taxane-based)	- IV infusion with strong evidence in mHSPC - May be preferred for aggressive disease	- More side effects (nausea, infection, hair loss) - Needs hospital visits - Fatigue

In the ENZA-pstudy, the combination of enzalutamide and [¹⁷⁷Lu]Lu-PSMA-617demonstrated a median overall survival (OS) of 34 months (95% CI:30–37), compared to 26 months (95% CI: 23–31) for enzalutamide alone. Thisrepresents an 8-month improvement in median OS and a 45% reduction inthe risk of death (hazard ratio [HR]: 0.55; 95% CI: 0.36–0.84; p=0.005). PubMed+4Targeted Oncology+4ScienceDirect+4

Notably, 38%of patients in the enzalutamide-only group received subsequent[¹⁷⁷Lu]Lu-PSMA-617 treatment off-trial, which may have influenced the survivaloutcomes. Oncology Nursing News+1Targeted Oncology+1

These findingssuggest that adding [¹⁷⁷Lu]Lu-PSMA-617 to enzalutamide offers a significantsurvival benefit over enzalutamide alone in patients with metastaticcastration-resistant prostate cancer (mCRPC).