Pocenbrodib for Prostate Cancer

(P300 Trial)

Recruiting at 13 trial locations

Overseen By Steve Kye, MD. MPH

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Pathos AI, Inc.

Must not be taking: Chemotherapy, Enzalutamide, Apalutamide, others

Disqualifiers: Small cell histology, Liver metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

252 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Pocenbrodib for prostate cancer that has spread and no longer responds to standard hormone treatments. Researchers aim to determine the best dose and assess whether Pocenbrodib is more effective alone or in combination with other drugs like Abiraterone acetate, Olaparib, or 177Lu-PSMA-617. Men diagnosed with metastatic prostate cancer, confirmed through imaging tests, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapy, investigational agents, or other anticancer drugs, including enzalutamide, apalutamide, or darolutamide, at least 14 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have tested Pocenbrodib for safety in individuals with advanced prostate cancer. Although detailed safety information remains limited, researchers aim to determine the safest dose, indicating that the treatment's safety is still under investigation. For Pocenbrodib combined with other drugs like Abiraterone acetate and Olaparib, clear safety information is not yet available, but these combinations are also under careful study.

Large clinical trials have shown that 177Lu-PSMA-617 is generally safe when used with other treatments. However, the safety of combining it specifically with Pocenbrodib is still being explored.

Overall, as this trial is in its early stages, researchers continue to gather safety evidence for Pocenbrodib and its combinations. This phase of research focuses on understanding the tolerability of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pocenbrodib for prostate cancer because it introduces a novel approach compared to standard treatments like hormone therapy, chemotherapy, or radiopharmaceuticals. Pocenbrodib stands out due to its potential to be used alone or in combination with other advanced therapies like abiraterone acetate, olaparib, or 177Lu-PSMA0617, potentially enhancing effectiveness. Additionally, its unique dosing regimen of 5 days on followed by 2 days off allows for flexibility and might reduce side effects, which is not typical with more continuous standard treatments. This combination of innovative mechanisms and flexible dosing has the potential to improve outcomes for patients with prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that Pocenbrodib, a type of drug, is under study for its potential to slow the progression of prostate cancer. Early studies found that it can lower levels of prostate-specific antigen (PSA), a marker used to monitor prostate cancer. This trial tests Pocenbrodib both as a monotherapy and in combination with other treatments like Abiraterone acetate, Olaparib, or 177Lu-PSMA-617. Each combination aims to improve treatment by attacking cancer cells in different ways. Initial results suggest these combinations could be promising for treating advanced prostate cancer that no longer responds to hormone therapy, but further research is needed to confirm these benefits. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for patients with metastatic castration-resistant prostate cancer. Specific eligibility criteria are not provided, but typically include factors like age, health status, and progression of disease.

Inclusion Criteria

My prostate cancer is confirmed by tissue analysis.

My cancer has spread, confirmed by recent scans.

Exclusion Criteria

I have liver metastases confirmed by tests.

I haven't taken any cancer drugs, including enzalutamide, apalutamide, or darolutamide, in the last 14 days.

My latest prostate biopsy showed signs of small cell or neuroendocrine cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Pocenbrodib monotherapy at multiple, sequential five rising doses (50, 100, 150, 200, and 250mg) using a QD dosing schedule of 5 days on/2 days off

28 days per dose level

Phase 2a Treatment

Participants receive Pocenbrodib monotherapy or in combination with Abiraterone acetate, Olaparib, or 177Lu-PSMA-617

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• Abiraterone Acetate
• Olaparib
• Pocenbrodib

Trial Overview The study is testing the safety and initial effectiveness of Pocenbrodib alone or combined with Abiraterone acetate, Olaparib, or 177Lu-PSMA-617 in treating advanced prostate cancer.

How Is the Trial Designed?

Group I: Phase 2 portion Experimental Treatment 2 Interventions

Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617

Group II: Phase 1 Portion Experimental Treatment 1 Intervention

Dose level 1: 50 mg QD (5 days on/2 days off) Dose level 2: 100 mg QD (5 days on/2 days off) Dose level 3: 150 mg QD (5 days on/2 days off) Dose level 4: 200 mg QD (5 days on/2 days off) Dose level 5: 250 mg QD (5 days on/2 days off)

Who Is Running the Clinical Trial?

Pathos AI, Inc.

Lead Sponsor

Trials

1

Recruited

250+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a review of seven randomized controlled trials involving 7103 patients with castration-resistant prostate cancer, abiraterone was found to significantly increase the risk of both any grade (RR = 1.34) and severe grade (RR = 1.71) cardiac disorders.

Enzalutamide was associated with a much higher risk of developing any grade (RR = 2.66) and severe grade (RR = 2.79) hypertension, indicating that while both drugs have cardiovascular risks, they affect different aspects of heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses. Lee, HY., Chen, HL., Teoh, JY., et al.[2022]

Cediranib showed some anti-tumor activity in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel treatment, with 43.9% of patients remaining progression-free at 6 months and a median progression-free survival of 3.7 months.

The treatment was generally well tolerated, with common side effects including hypertension and fatigue; however, adding prednisone helped reduce some of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. Dahut, WL., Madan, RA., Karakunnel, JJ., et al.[2023]

In prostate cancer, combining the SRC kinase inhibitor saracatinib with the hormonal therapy enzalutamide shows strong synergy in cell lines that express both full-length androgen receptors (AR-FL) and androgen receptor variants (AR-Vs), potentially improving treatment outcomes for patients with castration-resistant prostate cancer (CRPC).

The combination of saracatinib and enzalutamide not only decreases phosphorylation of key residues on androgen receptors but also leads to reduced DNA replication and increased apoptosis in cancer cells, suggesting a promising new strategy for enhancing the efficacy of existing therapies in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC. White, RE., Bannister, M., Day, A., et al.[2023]

MYB is activated in prostate cancer cells when treated with androgen deprivation therapy, and silencing MYB can inhibit cancer growth in both cell cultures and mouse models, suggesting it plays a key role in tumor progression.

Targeting the DNA damage response pathway, particularly through the inhibition of MYB and other related proteins, enhances the effectiveness of PARP inhibitors like olaparib, offering a potential new treatment strategy for advanced prostate cancer that has become resistant to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer. Li, L., Chang, W., Yang, G., et al.[2021]

In prostate cancer, combining the SRC kinase inhibitor saracatinib with the hormonal therapy enzalutamide shows strong synergy in cell lines that express both full-length androgen receptors (AR-FL) and androgen receptor variants (AR-Vs), potentially improving treatment outcomes for patients with castration-resistant prostate cancer (CRPC).

The combination of saracatinib and enzalutamide not only reduces DNA replication but also significantly increases apoptosis in cancer cells, suggesting a more effective therapeutic strategy compared to using saracatinib with chemotherapy (docetaxel).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saracatinib synergizes with enzalutamide to downregulate androgen receptor activity in castration resistant prostate cancer. White, RE., Bannister, M., Day, A., et al.[2023]

PARP inhibitors (PARPi) combined with androgen receptor signaling inhibitors (ARSI) show significant benefits in treating metastatic castration-resistant prostate cancer (mCRPC), as demonstrated in the TALAPRO-2 and PROpel trials, which included both HRR-mutated and HRR-non-mutated patients.

The combination therapy works at a molecular level by inducing a state similar to homologous recombination repair deficiency, leading to synthetic lethality where DNA damage accumulates and cannot be repaired, ultimately causing cancer cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double trouble for prostate cancer: synergistic action of AR blockade and PARPi in non-HRR mutated patients. Giesen, A., Baekelandt, L., Devlies, W., et al.[2023]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

The study developed a computational algorithm called 'secDrugs' to identify potential new treatments for lethal metastatic prostate cancer, focusing on the NAMPT pathway, which is overexpressed in drug-resistant cancer cells.

The drug FK866, which targets NAMPT, showed significant efficacy in reducing cancer cell invasion and motility, and it also improved treatment outcomes when combined with standard therapies like taxanes and AR-inhibitors, suggesting it could be a promising option for overcoming drug resistance in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Pharmacogenomics Data-Driven Computational Drug Prediction with Single-Cell RNAseq to Demonstrate the Efficacy of a NAMPT Inhibitor against Aggressive, Taxane-Resistant, and Stem-like Cells in Lethal Prostate Cancer. Mazumder, S., Mitra Ghosh, T., Mukherjee, UK., et al.[2022]

In the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06785636

NCT06785636 | Open-Label Study of Pocenbrodib Alone ... This is a dose-finding study to assess the safety and preliminary antitumor activity of Pocenbrodib alone or with Abiraterone acetate, Olaparib or 177Lu-PSMA- ...

2. urologytimes.com urologytimes.com/view/trial-launches-of-cbp-p300-inhibitor-in-mcrpc

Trial launches of CBP/p300 inhibitor in mCRPC The primary outcome measures include safety, objective response rate, and prostate-specific antigen (PSA) decline. The study will also be used ...

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/pathos-ai-doses-first-patient-in-pocenbrodib-trial/

Pathos AI Doses First Patient in Pocenbrodib Trial The study's primary objectives are to evaluate the safety, objective response rate, PSA decline, and pharmacokinetic/pharmacodynamic profile of ...

4. curetoday.com curetoday.com/view/first-patent-dosed-with-pocenbrodib-in-trial-for-metastatic-prostate-cancer

First Patent Dosed With Pocenbrodib in Trial for Metastatic ... The study is expected to enroll approximately 203 patients with metastatic castration-resistant prostate cancer who have progressed despite ...

5. withpower.com withpower.com/trial/pocenbrodib-for-prostate-cancer-e645a

Pocenbrodib for Prostate Cancer (P300 Trial) The drug FK866, which targets NAMPT, showed significant efficacy in reducing cancer cell invasion and motility, and it also improved treatment outcomes when ...

6. memorialcare.org memorialcare.org/professionals/research-clinical-trials/577-25-study-test-safety-and-early-effects-pocenbrodib-alone

A Study to Test the Safety and Early Effects of Pocenbrodib ... This clinical trial is testing a new treatment called Pocenbrodib to see how safe it is and whether it might help men with advanced prostate cancer that has ...