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Metastatic Prostate CancerPhase 1NCT04846478

Phase Ia/Ib Talazoparib + Tazemetostat for mCRPC

A Phase 1 study testing Talazoparib and Tazemetostat in people with Metastatic Prostate Cancer and Metastatic Castration-resistant Prostate Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This trial is testing whether molecularly targeted oral medications called talazoparib and tazemetostat can be safely combined for the treatment of prostate cancer, and whether the combination is effective in shrinking or preventing the growth of metastatic prostate cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Talazoparib and Tazemetostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
28 Jun 2021to 30 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed prostate cancer (code 10036910) with progressive disease at the time of study entry by either
  • Sequence of at least 2 rising PSA values at a minimum of 1-week intervals
  • Radiographic progression per RECIST1.1 for soft tissue and/or per PCWG3 for bone, with or without PSA progression
  • Patients must have metastatic disease by bone scintigraphy or other nodal or visceral lesions on CT or MRI with a bone or soft tissue lesion amenable to image-guided percutaneous biopsy, a castrate level of testosterone (<50ng/dL), and evaluable for disease response by either
  • Baseline PSA ≥ 2.0 ng/mL OR
  • Measurable disease per RECIST 1.1 NOTE: Subjects must maintain a castrate state. If they have not had an orchiectomy, they must continue to receive LHRH or GnRH agonists or antagonists unless intolerant.
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  • Past progression on at least one novel hormonal therapy (abiraterone, enzalutamide, apalutamide, darolutamide, galeterone, orteronel, seviteronel or equivalent) in either the hormone-sensitive or castration-resistant disease setting.
  • Not a candidate for docetaxel or cabazitaxel chemotherapy due to:
  • progression within 12 months of completion or intolerance to prior taxane OR
  • refusal of taxane OR
  • contraindication to, or lack of fitness for taxane OR
  • investigator assessment that taxane is not clinically indicated or preferred
  • Age ≥18 years. Children under 18 are excluded from this study as prostate cancer is a disease of adults
  • ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
  • Participants must have adequate organ and marrow function as defined below:
  • leukocytes ≥ 3,000/mcL
  • absolute neutrophil count ≥1,500/mcL
  • hemoglobin ≥9 g/dL (without transfusion or growth factor in prior 28 days)
  • platelets ≥ 100,000/mcL (without transfusion of growth factor in prior 28 days)
  • total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) unless known or suspected Gilbert syndrome
  • AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
  • glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 (based on Cockcroft-Gault formula OR creatinine clearance based on 24 hour urine collection)
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy (with no known or predicted drug-drug interactions with talazoparib and/or tazemetostat) with undetectable viral load within 6 months are eligible for this trial.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable. If suppressive therapy is indicated, there must be no known or predicted drug-drug interactions with talazoparib and/or tazemetostat.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if there are no known or predicted drug-drug interactions with talazoparib and/or tazemetostat and they have an undetectable HCV viral load.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Prior treatment with a PARP inhibitor is allowed.
  • Planned to undergo core biopsy of a recurrent/metastatic lesion adequate for next generation sequencing (NGS) after trial registration but prior to cycle 1 day 1 of therapy. Confirmation of adequacy of this biopsy material for NGS is NOT required for initiation of therapy. If elective biopsies are not being performed at the treating institution due to preparations or precautions related to COVID-19, this requirement can be waived on discussion with the trial PI.
  • Willing to undergo core biopsy of a recurrent/metastatic lesion adequate for next generation sequencing (NGS) after 8 weeks (+/- 7 days) of study treatment.
  • The effects of talazoparib and tazemetostat on the developing human fetus are unknown. For this reason and because oral chemotherapeutic agents are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of talazoparib and tazemetostat administration.
  • Ability to swallow oral medications.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Participants who have had chemotherapy, intravenous experimental agent, radiopharmaceutical therapy or radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
  • Participants who have received oral anti-neoplastic intervention such as an oral hormonal agent, PARP inhibitor, or oral experimental agent within 14 days prior to planned cycle 1 day 1 of study treatment.
  • Participants who have not recovered from clinically significant adverse events due to prior anti-cancer therapy (i.e., have clinically significant residual toxicities > Grade 1) except for stable complications of prior procedures (such as urinary incontinence or erectile dysfunction) or Grade 2 anorexia, alopecia, neuropathy, and fatigue, for which resolution is not required.
  • Participants who are receiving any other investigational agents.
  • Participants previously treated with an inhibitor of EZH2.
  • Patients with known brain metastases or leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to talazoparib or tazemetostat.
  • Participants receiving the following concurrent medications:
  • Participants receiving the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil are ineligible. Participants receiving other P-gp inhibitors are not excluded but should be monitored for potential increased adverse reactions.
  • Participants receiving BCRP inhibitors are not excluded but should be monitored for potential increased adverse reactions.
  • Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A4 are ineligible.
  • Precaution is warranted with concomitant use of agents with a narrow therapeutic index that are substrates of CYP3A4 and/or P-gp.
  • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
  • Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and nursing women are excluded from this study because they do not develop prostate cancer.
  • Arterial or venous thromboembolic event within the last 3 months.
  • Concurrent active malignancy. Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject to be in remission, or any prior malignancy that was treated with curative intent (no evidence of disease for at least 3 years) are also permitted to enroll.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase Ia/Ib Study of Talazoparib in Combination With Tazemetostat in Metastatic Castration-resistant Prostate Cancer (mCRPC)

This trial is testing whether molecularly targeted oral medications called talazoparib and tazemetostat can be safely combined for the treatment of prostate cancer, and whether the combination is effective in shrinking or preventing the growth of metastatic prostate cancer.

The names of the study drugs involved in this study are:

  • Talazoparib
  • Tazemetostat
Read the detailed description

This is a Phase 1a/1b clinical trial to assess safety, tolerability and preliminary clinical activity of the combination of talazoparib with tazemetostat in metastatic castration-resistant prostate cancer (mCRPC) patients.

The U.S. Food and Drug Administration (FDA) has not approved talazoparib or tazemetostat for metastatic castration-resistant prostate cancer (mCRPC) but they have been approved for other uses. Talazoparib has been approved for use in breast cancer, and tazemetostat has been approved for use in certain types of sarcoma and lymphoma.

Talazoparib is an orally administered molecularly targeted chemotherapy drug called a "PARP inhibitor", which acts to block the ability of cancer cells to repair certain forms of damage to their DNA - the accumulation of damaged DNA causes certain cancer cells to die. Other PARP inhibitors are already approved for use in prostate cancer patients with specific gene mutations detected in their blood or in their cancer, and talazoparib is currently being studied for treatment of prostate cancer in other clinical trials.

Tazemetostat is an orally administered molecularly targeted chemotherapy drug called an "EZH2 inhibitor", which acts to block the production of proteins encoded by DNA in the cancer cells that are important in cancer growth and survival. Tazemetostat is also being studied for the treatment of prostate cancer in other clinical trials. In the laboratory setting, tazemetostat causes changes in protein levels in prostate cancer cells that make them sensitive to dying in the presence of PARP inhibitors.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

The study design involves two parts. The first part is called the "dose escalation" to find a safe dose for the combination of talazoparib and tazemetostat. The second part is called the "dose expansion" where additional participants are treated at the safe dose identified in the first part of the study.

Participants will receive study treatment for as long as they do not have serious side effects and their disease does not get worse. Participants will be followed after completion of study treatment for up to 24 months.

It is expected that about 38 people will take part in this research study.

Funding for this research is provided by a grant awarded by the non-profit Prostate Cancer Foundation along with Pfizer, Inc. In addition, Pfizer is supporting the study by providing the study drug talazoparib. Epizyme, Inc. is supporting the study by providing the study drug tazemetostat.

Being tested
Talazoparib, Tazemetostat
Keywords
Metastatic Prostate Cancer, Metastatic Castration-resistant Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TalazoparibDrug

    Also called Talzenna

    capsule, taken by mouth, once a day

  • TazemetostatDrug

    Also called Tazverik, EPZ-6438

    orally as a tablet twice daily.

Study groups in NCT04846478
Study groupRoleWhat they receive
Dose Escalation Talazoparib + TazemetostatExperimentalStandard 3+3 dose escalation will be followed, participants will initially receive talazoparib and tazemetostat at a dose of 75% of the starting dose for their FDA-approved indications. During each 28 day study treatment cycle participants will take: * Talazoparib once daily. * Tazemetostat twice daily.
Receives: Drug: Talazoparib; Drug: Tazemetostat
Dose Expansion Talazoparib + TazemetostatExperimentalParticipants will receive talazoparib and tazemetostat at the safe dose identified in the first part (dose escalation) of the study. During each 28 day study treatment cycle participants will take: * Talazoparib once daily. * Tazemetostat twice daily.
Receives: Drug: Talazoparib; Drug: Tazemetostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Dose Limiting Toxicity (DLT)

    Assessed by the investigator, based on toxicity grade (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), clinical significance, and possible relationship to either study drug.

    Measured: Enrollment up to 28 days

  2. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

    The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade.

    Measured: Enrollment up to 2 years

Secondary outcomes (1)

  1. Overall response rate (ORR)

    Assessed by RECIST 1.1 and/or prostate-specific antigen (PSA) reduction by ≥ 50%

    Measured: Enrollment up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2021
  2. Study start28 Jun 2021
  3. Primary completion25 Sep 2025
  4. Study completion30 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04846478
Sponsor's protocol ID
21-086
Status last verified
May 2026
First submitted
13 Apr 2021
Last updated
12 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Talazoparib and Tazemetostat in people with Metastatic Prostate Cancer and Metastatic Castration-resistant Prostate Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Dose Limiting Toxicity (DLT) (time frame: Enrollment up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04846478.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.

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