Mevrometostat + Enzalutamide for Prostate Cancer

Recruiting at 155 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Enzalutamide

Must not be taking: CYP3A4/5 inhibitors

Disqualifiers: Cardiovascular disease, Brain metastasis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

900 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use drugs that strongly affect certain liver enzymes (CYP3A4/5) during the study, except for enzalutamide.

What data supports the effectiveness of the drug Mevrometostat + Enzalutamide for prostate cancer?

Enzalutamide, a component of the treatment, has been shown to significantly improve survival in men with metastatic castration-resistant prostate cancer (mCRPC), reducing the risk of death by 37% in clinical trials. This suggests that enzalutamide is effective in treating this type of prostate cancer. ^{1 2 3 4 5}

Is the combination of Mevrometostat and Enzalutamide safe for humans?

Enzalutamide has been studied for safety in men with prostate cancer, showing that common side effects include fatigue and, in some cases, more severe issues like low platelet counts and seizures. However, specific safety data for Mevrometostat or its combination with Enzalutamide is not provided in the available research. ^{6 7 8 9 10}

How is the drug Mevrometostat + Enzalutamide different from other prostate cancer treatments?

The combination of Mevrometostat and Enzalutamide is unique because it pairs a novel drug, Mevrometostat, with Enzalutamide, a well-established treatment for prostate cancer, potentially offering a new approach to targeting cancer growth. ^{1 2 11 12 13}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for men with metastatic castration-resistant prostate cancer (mCRPC) who haven't previously been treated with ARSi or abiraterone. Participants should meet other study requirements to join.

Inclusion Criteria

My cancer has worsened despite hormone therapy or surgery.

I am a man aged 18 or older.

My prostate cancer is confirmed without small cell features.

Exclusion Criteria

Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study

Previous administration with an investigational product (drug or vaccine) within 30 days

I have not received chemotherapy for my metastatic castration-resistant prostate cancer, except for first-generation antiandrogens or Docetaxel for metastatic castration-sensitive prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization

Participants are randomized to receive either PF-06821497 with enzalutamide or placebo with enzalutamide

Treatment

Participants receive either PF-06821497 in combination with enzalutamide or placebo in combination with enzalutamide

Up to 3 years

Safety Follow-up

Participants are monitored for safety and adverse events

Up to 5 years

Long-Term Follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 5 years

Treatment Details

Interventions

• PF-06821497

Trial Overview The study tests if PF-06821497 combined with enzalutamide is more effective than enzalutamide alone in treating mCRPC. Some participants will receive a placebo instead of PF-06821497.

Participant Groups

Group I: Arm A Experimental Treatment 2 Interventions

Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)

Group II: Arm B Active Control 2 Interventions

Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Enzalutamide is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC), approved for use both after chemotherapy and before chemotherapy, significantly improving patient survival.

The STRIVE Phase II clinical trial demonstrated that enzalutamide outperforms bicalutamide in patients with nonmetastatic and mCRPC who have not responded to androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of enzalutamide on the treatment of prostate cancer. Nadal, R., Bellmunt, J.[2021]

The KEYNOTE-641 study is a Phase III clinical trial designed to evaluate the safety and efficacy of combining the PD-1 inhibitor pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC).

This trial aims to determine if the combination therapy can improve outcomes compared to enzalutamide alone, addressing the need for more effective treatments in a patient population with a median survival of about 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Graff, JN., Liang, LW., Kim, J., et al.[2021]

Enzalutamide is an effective and well-tolerated treatment for Italian patients with hormone-refractory metastatic castration-resistant prostate cancer who have progressed after chemotherapy, as demonstrated in a study of 60 patients.

The treatment led to a significant reduction in serum prostate-specific antigen (PSA) levels, which correlated with improved overall survival, indicating that PSA levels can be a predictive marker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Efficacy of Enzalutamide in Metastatic Prostate Cancer: Prospective Single-center Study. Cicero, G., DE Luca, R., Dorangricchia, P., et al.[2021]

In the PREVAIL study involving 872 men with metastatic castration-resistant prostate cancer, significant declines in prostate-specific antigen (PSA) levels after 3 months of enzalutamide treatment were linked to improved overall survival and progression-free survival outcomes.

Specifically, 88% of patients experienced a PSA decline of at least 30%, and greater declines were associated with longer survival and better quality of life, indicating that monitoring PSA levels can provide valuable prognostic information for treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial. Armstrong, AJ., Lin, P., Higano, CS., et al.[2021]

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]

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]

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 study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

In a real-world study involving 1732 men with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide demonstrated a median time to treatment failure of 12.9 months for patients who had not previously received chemotherapy or abiraterone, compared to 8.4 months for those who had, indicating its efficacy in different treatment settings.

The safety profile of enzalutamide was consistent with previous clinical trials, with treatment-emergent adverse events reported in 51.0% of chemotherapy-naïve patients and 62.2% of post-chemotherapy patients, with fatigue being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. Payne, H., Robinson, A., Rappe, B., et al.[2022]

In a phase 2 study involving 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Tombal, B., Borre, M., Rathenborg, P., 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]

In a phase 3 trial involving 1199 men with castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed superior efficacy in secondary outcomes, including a 54% reduction in PSA levels and improved quality of life, although it was associated with higher rates of fatigue and other side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival with enzalutamide in prostate cancer after chemotherapy. Scher, HI., Fizazi, K., Saad, F., et al.[2022]

Enzalutamide has been proven effective in increasing overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously undergone docetaxel chemotherapy, as demonstrated in the AFFIRM study.

The drug is generally well tolerated by patients, and ongoing trials, such as the PREVAIL study, are exploring its effectiveness in earlier treatment stages before chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of enzalutamide, a new hormonal therapy]. Beuzeboc, P., Benderra, MA., de La Motte Rouge, T.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The evolving role of enzalutamide on the treatment of prostate cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

The Clinical Efficacy of Enzalutamide in Metastatic Prostate Cancer: Prospective Single-center Study. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial. [2021]

5. China pubmed.ncbi.nlm.nih.gov

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

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

7. Switzerland 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. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Increased survival with enzalutamide in prostate cancer after chemotherapy. [2022]

13. France pubmed.ncbi.nlm.nih.gov

[Management of enzalutamide, a new hormonal therapy]. [2021]