Enzalutamide + M9241 for Recurrent Prostate Cancer

Overseen By Ravi A Madan, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Enzalutamide

Must not be taking: CYP2C8, CYP3A4 inhibitors

Disqualifiers: Soft tissue disease, Bone lesions, Seizures, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better treatments for prostate cancer that returns after initial treatment. Researchers are testing enzalutamide alone and in combination with another drug, M9241 (also known as NHS-IL12). The goal is to determine if these treatments can more effectively manage recurrent prostate cancer. The trial seeks participants with prostate cancer that has returned after surgery or radiation and who can still perform daily activities. Participants will take enzalutamide daily and may receive monthly M9241 injections, with regular check-ups over several months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on medications that strongly affect certain liver enzymes (CYP2C8 or CYP3A4).

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

Research shows that enzalutamide is usually well-tolerated. In previous studies, some side effects, such as falls, occurred in about 12% of patients, higher than the 6% seen with a placebo. However, enzalutamide has been used for prostate cancer before and is known to help patients live longer without the disease spreading.

Past research indicates that M9241 is generally safe and well-tolerated. Some patients experienced a drop in PSA levels, a protein linked to prostate cancer, which is a positive sign. The combination of M9241 with another drug also had manageable side effects.

These findings suggest that both enzalutamide and M9241 have been generally safe in previous studies. This trial tests their combined use, a new approach. Keep in mind that while these results are promising, participating in a trial can still involve unknown risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Enzalutamide combined with M9241 for recurrent prostate cancer because of its innovative approach to treatment. Unlike standard options like hormone therapy or chemotherapy, this combo harnesses the power of Enzalutamide to block androgen receptors, helping slow cancer growth. Additionally, the inclusion of M9241, an immunotherapy agent, aims to boost the body’s immune response against cancer cells. This dual mechanism offers a promising new direction that could enhance effectiveness and potentially improve outcomes for patients with recurrent prostate cancer.

What evidence suggests that this trial's treatments could be effective for recurrent prostate cancer?

Research has shown that enzalutamide, which participants in this trial may receive, effectively treats prostate cancer, particularly when the cancer has spread and other treatments have failed. Studies have found that it helps patients live longer and slows the disease's progression. In this trial, some participants will receive a combination of enzalutamide with M9241. Early signs suggest this combination could be promising. M9241 has been shown to be safe, and some patients have experienced a drop in PSA levels, indicating potential cancer shrinkage. Although information on M9241 alone is limited, using it with enzalutamide might enhance the immune system's ability to fight the cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Men aged 18+ with recurrent prostate cancer after primary treatment, a rising PSA level, and PSMA PET/CT scan evidence of cancer. They must have adequate organ function, agree to contraception use post-treatment for 3 months, and be able to swallow pills. Excluded are those with certain other medical conditions or allergies related to the study drugs.

Inclusion Criteria

Creatinine < 1.5 X institution ULN

Prostate-specific antigen (PSA) doubling time within less than 12 months.

Testosterone >100 ng/dL.

Exclusion Criteria

Evidence of bone lesions on Tc99 bone scan.

I am on long-term steroids or other drugs that weaken my immune system.

My scans show cancer in soft tissues, meeting specific size criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive enzalutamide or enzalutamide plus M9241 in 4-week cycles for 3 cycles

12 weeks

3 visits (in-person, monthly)

Re-treatment

Participants who experience PSA recovery to baseline may receive a second course of enzalutamide treatment for 3 additional cycles

12 weeks

3 visits (in-person, monthly)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits every 6 weeks for up to 5 years

5 years

Visits every 6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• M9241

Trial Overview The trial is testing enzalutamide (a daily pill) alone and combined with M9241 (a monthly injection), in men whose prostate cancer has returned. Participants will undergo cycles of treatment followed by regular clinic visits for monitoring up to five years.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 2 Interventions

Enzalutamide+PDS01ADC

Group II: Arm 1 Experimental Treatment 1 Intervention

Enzalutamide

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

Enzalutamide has been shown to significantly improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), both in those who have not received chemotherapy and those who have been pretreated with docetaxel, based on results from large phase III trials.

The current treatment landscape for mCRPC has expanded beyond just docetaxel to include various therapies, but there is still a need for direct comparisons between these treatments to determine the best sequence for patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of enzalutamide in the treatment of advanced prostate cancer. Ciccarese, C., Nobili, E., Grilli, D., et al.[2021]

In a phase III trial involving patients with metastatic, castration-resistant prostate cancer (mCRPC) who had progressed after docetaxel treatment, enzalutamide significantly improved overall survival, with a median survival of 18.4 months compared to 13.6 months for placebo, indicating a 37% reduction in mortality risk.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although there is a small, dose-dependent risk of seizures; it also improved quality of life and pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Sanford, M.[2021]

Enzalutamide (Enz) was evaluated in a retrospective study of 47 men with heavily pretreated metastasized castration-resistant prostate cancer (mCRPC), showing a 23% response rate with significant PSA declines, indicating its potential efficacy even in later treatment lines.

The treatment was generally well tolerated, with common side effects like fatigue and nausea, and resulted in a median overall survival of 40.1 weeks and a median progression-free survival of 12.1 weeks, suggesting it can be a viable option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. Badrising, SK., van der Noort, V., Hamberg, P., et al.[2021]

Enzalutamide, a treatment for metastatic castration-resistant prostate cancer, was linked to a case of acute generalized exanthematous pustulosis (AGEP) in a 62-year-old male patient, indicating a potential skin-related side effect of this medication.

The patient's skin reaction occurred shortly after starting enzalutamide and resolved within four weeks, suggesting that the long half-life of enzalutamide (5.8 days) may contribute to the prolonged duration of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. Alberto, C., Konstantinou, MP., Martinage, C., et al.[2020]

Enzalutamide significantly improves overall survival in men with metastatic, castration-resistant prostate cancer (mCRPC), showing a 37% reduced risk of death compared to placebo, with median survival times of 18.4 months versus 13.6 months.

The results from the phase III AFFIRM trial support the continued targeting of the androgen receptor as an effective treatment strategy for prostate cancer, even after patients have developed resistance to castration therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide (formerly MDV3100) as a new therapeutic option for men with metastatic castration-resistant prostate cancer. Aragon-Ching, JB.[2021]

Enzalutamide (XTANDI) was approved by the FDA for treating metastatic castration-resistant prostate cancer based on a study of 1,199 patients, showing a significant improvement in overall survival (18.4 months for enzalutamide vs. 13.6 months for placebo).

The treatment was well-tolerated, with common side effects including fatigue and back pain, and a low incidence of seizures (0.9% in the enzalutamide group), indicating a favorable benefit-risk profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary. Ning, YM., Pierce, W., Maher, VE., et al.[2021]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

In a phase 3 trial involving 1401 men with nonmetastatic, castration-resistant prostate cancer, enzalutamide significantly improved median overall survival to 67.0 months compared to 56.3 months for placebo, indicating a 27% lower risk of death.

The safety profile of enzalutamide was consistent with previous studies, with a similar rate of serious adverse events compared to placebo, primarily involving fatigue and musculoskeletal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg, CN., Fizazi, K., Saad, F., et al.[2021]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

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Safety Profile in CSPC In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients ...

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Xtandi | European Medicines Agency (EMA) Patients treated with Xtandi lived for an average of 37 months without their disease becoming metastatic compared with 15 months on placebo.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622

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