We can't always win! 😐
"In the current study, interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements of disease, including prostate-specific antigen (PSA) levels, in the 20 patients treated in eight dosing cohorts with various doses and schedules of administration of ONCT-534. ONCT-534 was generally well tolerated, with dose limiting toxicity observed in 2 of 3 patients at the highest dose tested, 1200 mg given orally once per day."
That is to bad. I Feel for the warriors and thank them for doing the trial.
I really thought attacking the N terminal domain would stop all translations that involved the androgen receptor.
Do we know why it failed? I am wondering if the CRPC patients already had resistance via progesterone receptors or other non AR pathways. I hope they genetically mapped that prior to this treatment so we might gain some insight as to why it failed.
Here is AI on
ONCT-534 is an investigational drug developed by Oncternal Therapeutics, primarily aimed at treating metastatic castration-resistant prostate cancer (mCRPC). It works as a dual-action androgen receptor inhibitor (DAARI), meaning it targets both the ligand-binding domain (LBD) and the N-terminal domain (NTD) of the androgen receptor (AR). This dual mechanism is particularly significant as it addresses common resistance mechanisms seen in advanced prostate cancer, such as AR splice variants and LBD mutations, which are typically resistant to existing therapies like enzalutamide or abiraterone .
Preclinical studies have shown that ONCT-534 has promising anti-tumor activity in models resistant to other AR-targeted therapies, making it a potential treatment for patients who have relapsed or are refractory to current AR inhibitors . Additionally, the drug has received FDA fast-track designation, which will help expedite its development and review due to the significant unmet need for effective treatments in mCRPC .
Currently, ONCT-534 is being evaluated in a phase 1/2 clinical trial, where its safety, tolerability, and anti-tumor activity are being assessed in patients with advanced prostate cancer .
Disappointed😞! I had my fingers crossed for this one.
Things changed a bit:
"Based on initial pharmacokinetic results, two additional dosing cohorts with twice daily (BID) oral dosing of ONCT-534 had been incorporated in the Phase 1/2 study ONCT-534-101 (NCT05917470). Overall, fifteen patients received ONCT-534 once daily (QD) in six dosing cohorts and six patients received ONCT-534 BID in two dosing cohorts. Based on a data cut off of September 30, 2024, the BID dosing schedule was well tolerated, with no related Grade 3 or higher toxicities. One patient, who experienced a rising PSA on ONCT-534 at 160 mg BID, had a subsequent 50% reduction in PSA after four weeks of ONCT-534 at 300 mg BID, and at the same time the CAT Scan showed a 16% reduction in target lesions compared to baseline. Enumeration and biomarker analysis of circulating tumor cells (CTCs) showed promising effects on expression of androgen receptor (AR)-regulated genes, and AR nuclear translocation in six additional patients. CTC analysis also showed that some patients who did not respond to ONCT-534 had prostate cancer that had developed neuroendocrine features, which are associated with AR independent disease."
Phase 1 trial shows promising results for fractionated dose of 225Ac-J591 in PCa treatment
Good News! But what about the joints (ankles, knees, elbows)?
Psilocybin for depression, anxiety and fear of death in advanced cancer patients.
Help with choosing treatment pathway
Current Understanding of Resistance to Abiraterone and Enzalutamide in Advanced PCa
