Phase 2 trial will start soon: opaganib plus darolutamide for mCRPC

[Maxone73]

A phase 2 clinical trial will start to assess the combination of opaganib (ABC294640) and darolutamide (Nubeqa) in patients with metastatic castration-resistant prostate cancer (mCRPC). The study plans to enroll 80 participants, utilizing the PCPro lipid biomarker test to identify individuals who may benefit from this therapy.

Eligible patients will be randomly assigned to receive either darolutamide with a placebo or darolutamide combined with opaganib. Opaganib, a sphingosine kinase-2 (SPHK2) inhibitor, targets specific cancer cell pathways, potentially overcoming resistance to androgen receptor pathway inhibitors.

The primary endpoint is 12-month radiographic progression-free survival. Notably, individuals previously treated with potent androgen receptor inhibitors are excluded from the trial.

I am not an expert, but I do not like the design of this trial. It's hard nowadays to find someone who is metastatic and castration resistant that has not used darolutamide, enzalutamide, abiraterone or another ARSI in single, double or triple therapy at least when he was hormone sensitive.

Plus they could kill 3 birds with one stone if they added:

1 - opaganib + ARSI in people who have been treated with an ARSI for at least 2 years and are still hormone sensitive (but approaching resistance, this would help to understand how long it can delay resistance)

2 - opaganib + darolutamide in people already using daro who became resistant (to see if it can not only prevent but reverse resistance)

But ok...

prostatewarriors.com/2025/0...

[dhccpa]

It always discourages me a bit to see clinical trials to make ADT or ARSI work better, rather than a sea change with dramatic reversal of the disease. But oh well....

[Maxone73 in reply to dhccpa]

Un colpo al cerchio e uno alla botte! The suggested translation is "Having a foot in both camps". We need anything that can keep us "frozen" while promising but early stage science finds the optimal solution IMO 😀😀

[dhccpa in reply to Maxone73]

Fair enough! And I do appreciate the poster behind this constantly emerging news. Always worth reading!

[Maxone73 in reply to dhccpa]

oh I will do more and more!

[gsun]

I agree with you saying how can they find enough people who are resistant who have not used one of those drugs? But your #1 study scenario is a difficult one because how can you tell if you are still sensitive but approaching resistance? I am there now but I suspect i am already resistant. PSA going up but not dramatically.

[MWPesaPharmD in reply to gsun]

Unfortunately ADT monotherapy in mHSPC remains rather entrenched in the real-world, although not in clinical guidelines, so there are plenty of patients to potentially recruit.

ascopubs.org/doi/10.1200/JC...

[gsun in reply to MWPesaPharmD]

Wow, that’s unfortunate.

[Maxone73 in reply to gsun]

You can do that only statistically. If PSA is stable for 3 consecutive months and you are 24 months into the therapy you are likely still hormone sensitive but approaching resistance (statistically). This was true with old drugs, after 24 months you were likely to become CR. I do not remember data from ARANOTE trial (doublet) but it was similar to ARASENS and in ARASENS median castration resistance was not reached after a median follow‐up period of approximately 43 months. So I would think that taking someone 2 years into ADT+daro would be a decently safe bet.