PF-06821497 + Enzalutamide for Prostate Cancer

(MEVPRO-1 Trial)

Recruiting at 156 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Pfizer

Must not be taking: Chemotherapy, ARSi, PARP, others

Disqualifiers: Cardiovascular disease, Brain metastasis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Pfizer MEVPRO-1 (C2321014) is a randomized, open-label, multi-center clinical trial evaluating whether combining the study medicine (PF-06821497) with enzalutamide is safe and effective compared to physician's choice of either second-line androgen receptor (AR) directed therapy with enzalutamide or docetaxel (chemotherapy) for treating metastatic castration-resistant prostate cancer (mCRPC) after progression on prior abiraterone acetate treatment. The primary objective of this clinical trial is to assess the radiographic progression free survival (rPFS) of the combination of PF-06821497 plus enzalutamide versus physician's choice of enzalutamide or docetaxel.

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 have had certain prostate cancer treatments like enzalutamide or chemotherapy before. You should discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug PF-06821497 + Enzalutamide for prostate cancer?

Research shows that enzalutamide, a part of this drug combination, improves survival in men with metastatic castration-resistant prostate cancer (mCRPC), both after chemotherapy and in chemotherapy-naive patients. This suggests that enzalutamide is effective in treating advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of PF-06821497 and Enzalutamide safe for humans?

Enzalutamide has been studied extensively and generally shows a favorable safety profile, though it can cause side effects like fatigue, diarrhea, back pain, hot flashes, and high blood pressure. Few seizures have been reported, and breast-related disorders have been noted. There is no specific safety data available for PF-06821497 in the provided research. ^{2 3 6 7 8}

What makes the drug PF-06821497 + Enzalutamide unique for prostate cancer treatment?

PF-06821497 combined with Enzalutamide is unique because it pairs a novel drug, PF-06821497, with Enzalutamide, a well-established androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway, which is crucial for prostate cancer growth. This combination may offer a new approach by potentially enhancing the effectiveness of Enzalutamide in treating prostate cancer. ^{1 2 4 7 9}

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 have previously been treated with Abiraterone Acetate. Participants should not have received certain other treatments and must meet specific health criteria.

Inclusion Criteria

I am castrated with low testosterone levels.

I can care for myself and my doctor believes I have at least 6 months to live.

My prostate cancer is confirmed without being a small cell type.

Exclusion Criteria

I have liver problems.

Any medical (including active or clinically significant bacterial, fungal or viral infection) 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

I have a serious heart condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-06821497 in combination with enzalutamide or physician's choice of enzalutamide or docetaxel

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

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

Up to approximately 4.5 years

Treatment Details

Interventions

• PF-06821497 (Epigenetic Modulator)

Trial Overview The study is testing the safety and effectiveness of a new medicine, PF-06821497, combined with Enzalutamide compared to the standard treatment choice of either Enzalutamide alone or Docetaxel chemotherapy in treating mCRPC after prior treatment failure.

Participant Groups

Group I: Arm A Experimental Treatment 2 Interventions

Investigational Arm A: PF-06821497 875 mg twice daily (BID) + enzalutamide 160 mg every day (QD)

Group II: Arm B Active Control 2 Interventions

Comparator Arm B: Physician's choice of enzalutamide 160 mg QD or docetaxel 75 mg/m2 intravenous (IV) every 21 days

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 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]

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]

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]

In the final analysis of the PREVAIL study, enzalutamide significantly improved overall survival in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), reducing the hazard of death by 17% compared to placebo, with a median overall survival of 36 months versus 31 months.

However, there was a slightly higher incidence of fatal treatment-emergent adverse events with enzalutamide, including an increase in fatal cardiovascular events (1.6% vs 0.4%), indicating a need to balance survival benefits with potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial. Armstrong, AJ., Lin, P., Tombal, B., et al.[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]

Enzalutamide significantly improves survival and delays skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC), as shown in the phase III AFFIRM study with consistent benefits across all subgroups.

In the phase III PREVAIL study, enzalutamide reduced the risk of radiographic progression and death in chemotherapy-naïve mCRPC patients, while also demonstrating a favorable safety profile with similar adverse event rates compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. Merseburger, AS., Haas, GP., von Klot, CA.[2020]

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 long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial. [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. England pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. [2020]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. [2021]