ODM-208 for Prostate Cancer

(CYPIDES Trial)

Not currently recruiting at 19 trial locations

Overseen By Orion Corporation, CSD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Orion Corporation, Orion Pharma

Must be taking: GnRH analogue

Disqualifiers: Brain metastases, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ODM-208, for men with a specific type of prostate cancer that has spread and does not respond to standard hormone treatments. The main goal is to assess the drug's safety and tolerability. The trial includes different parts, examining how the drug interacts with other medications and determining the best dose. Men with metastatic prostate cancer that resists castration (treatment to lower testosterone) and who have tried other hormone therapies might be suitable candidates. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing androgen deprivation therapy is required, so you should continue with that treatment.

Is there any evidence suggesting that ODM-208 is likely to be safe for humans?

Research has shown that ODM-208 is reasonably safe for men with advanced prostate cancer that no longer responds to standard hormone therapy. In earlier studies, patients handled the treatment well without major safety concerns. Although some side effects occurred, they were generally manageable. This suggests that ODM-208 is safe enough for further testing in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Most treatments for prostate cancer involve hormone therapies that target androgens, like testosterone, to slow cancer growth. But ODM-208 works differently. It's an innovative drug that blocks the production of all steroid hormones, not just androgens, at a very early stage. This comprehensive approach could potentially stop cancer cells from accessing the hormones they need to grow, offering new hope for patients, especially those for whom other treatments have stopped working. Researchers are enthusiastic because this could lead to a more effective way to manage advanced prostate cancer.

What evidence suggests that ODM-208 might be an effective treatment for prostate cancer?

Research has shown that ODM-208, a treatment for advanced prostate cancer, yields promising results. In earlier studies, ODM-208 significantly blocked the production of certain hormones that often promote prostate cancer growth. Approximately 53-56% of patients taking ODM-208 experienced a 50% reduction in PSA levels, while 69-70% saw a 30% reduction. These findings suggest that ODM-208 effectively lowers hormone levels, potentially slowing cancer growth. Participants in this trial will join different study arms, including dose escalation, dose expansion, and drug-drug interaction assessments, to further evaluate ODM-208's effectiveness and safety. ^{2 3 4 6 7}

Who Is on the Research Team?

Karim Fizazi

Principal Investigator

Gustave Roussy, Cancer Campus, Grand Paris

Are You a Good Fit for This Trial?

This trial is for men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread. They should have tried at least one hormonal treatment like abiraterone or enzalutamide, and possibly chemotherapy. Good physical condition (ECOG 0-1) is required, along with normal organ function. Men must be on hormone-lowering treatments or had surgery to remove testicles.

Inclusion Criteria

I am currently on hormone therapy for cancer or have had both testicles removed.

My blood, liver, and kidney tests are within normal ranges.

My cancer has spread to other parts of my body.

Exclusion Criteria

I do not have any active heart or brain blood vessel problems.

I have a condition or infection that makes taking steroids unsafe.

I have brain metastases or active leptomeningeal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ODM-208 to evaluate safety and tolerability

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ODM-208

Trial Overview The study tests ODM-208, a new drug for advanced prostate cancer that doesn't respond to standard hormone treatments anymore. It looks at how safe the drug is and how it moves through the body when taken by mouth. Some patients will also receive Midazolam as part of the study.

How Is the Trial Designed?

Group I: ODM-208 Part 2 Drug drug interaction Experimental Treatment 2 Interventions

Group II: ODM-208 Part 2 Dose expansion Experimental Treatment 1 Intervention

Group III: ODM-208 Part 1 Dose escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Orion Corporation, Orion Pharma

Lead Sponsor

Trials

140

Recruited

45,200+

Liisa Hurme

Orion Corporation, Orion Pharma

Chief Executive Officer since 2022

PhD in Biochemistry, University of Helsinki

Hilpi Rautelin

Orion Corporation, Orion Pharma

Chief Medical Officer since 2023

MD, University of Turku

Published Research Related to This Trial

ODM-201, an androgen receptor inhibitor, was found to be safe and well-tolerated in men with metastatic castration-resistant prostate cancer, with no dose-limiting toxic effects reported during the trial involving 24 patients in phase 1.

At 12 weeks, 29% to 33% of patients across different dosage groups (200 mg, 400 mg, and 1400 mg) showed a significant PSA response, indicating that ODM-201 effectively suppresses disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Fizazi, K., Massard, C., Bono, P., et al.[2017]

ODM-201, a second-generation androgen receptor inhibitor, demonstrated similar pharmacokinetics between its tablet and capsule formulations, indicating that the tablet can be effectively used in treatment.

In a trial with 30 chemotherapy-naive men with metastatic castration-resistant prostate cancer, 83% showed a significant PSA response (≥50% reduction), and the treatment was well tolerated, with common side effects being fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study. Massard, C., Penttinen, HM., Vjaters, E., et al.[2018]

Extended treatment with ODM-201, an androgen receptor antagonist, was well tolerated in 41 chemotherapy-naïve and CYP17 inhibitor-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), showing an overall adverse event incidence of 80.5%, mostly mild (grade 1-2).

The treatment demonstrated sustained antitumour activity, with median times to prostate-specific antigen (PSA) progression of 12.4 months and radiological progression of 15.3 months, indicating that ODM-201 could be a viable long-term therapeutic option for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Chemotherapy-naïve and CYP17 Inhibitor-naïve Patients: Follow-up from the ARADES and ARAFOR Trials. Shore, ND., Tammela, TL., Massard, C., et al.[2019]

In the ARADES trial involving 134 patients with castration-resistant prostate cancer (CRPC), prolonged treatment with the androgen receptor antagonist ODM-201 was well tolerated, showing a consistent safety profile with no unexpected adverse effects over an average treatment duration of 8.2 months.

Patients who had not previously undergone chemotherapy experienced significantly longer median times to PSA progression (25.2 months) and radiographic progression (14.0 months) compared to those who had been pretreated, suggesting that ODM-201 may be particularly effective in chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Castration-resistant, CYP17 Inhibitor-naïve Prostate Cancer: Results from Extended Follow-up of the ARADES Trial. Fizazi, K., Massard, C., Bono, P., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.159

MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with ... MK-5684 profoundly suppressed androgen synthesis resulting in PSA50 responses in 55.6% and 16.7% of patients and PSA30 responses in 69.8% and ...

2. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300171

Targeted Inhibition of CYP11A1 in Castration-Resistant ... In this phase 1/2 study, ODM-208 had a reasonable safety profile in men with metastatic castration-resistant prostate cancer who had progressed ...

3. urotoday.com urotoday.com/conference-highlights/asco-gu-2022/asco-gu-2022-prostate-cancer/135412-asco-gu-2022-phase-1-results-of-the-odm-208-first-in-human-phase-1-2-trial-in-patients-with-metastatic-castration-resistant-prostate-cancer-cypides.html

ASCO GU 2022: Phase 1 Results of the ODM-208 First-in- ... Dr. Fizazi concluded that treatment with ODM-208 among men with heavily pre-treated mCRPC was highly effective in blocking the production of steroid hormones.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03205-8/fulltext

1605P Opevesostat (MK-5684/ODM-208), an oral ... Opevesostat treatment led to PSA50 responses in 53.0% and 14.7% of patients, and PSA30 responses in 68.2% and 29.4% of patients, with and without AR-LBD ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT437212

MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with ... MK-5684 profoundly suppressed androgen synthesis resulting in PSA50 responses in 55.6% and 16.7% of patients and PSA30 responses in 69.8% and 30.0% of patients, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03436485

NCT03436485 | Safety and Pharmacokinetics of ODM-208 ... The purpose of this first-in-man study is to evaluate safety and tolerability of ODM-208 in patients with metastatic castration-resistant prostate cancer.

7. clin.larvol.com clin.larvol.com/trial-detail/NCT03436485

Safety and Pharmacokinetics of ODM-208 in Patients ... CYPIDES phase 1 data shows that ODM-208 effectively blocked the production of all steroid hormones in men with metastatic castration-resistant prostate cancer ( ...