Phase Ia/Ib Talazoparib + Tazemetostat for mCRPC

NCT04846478 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-086
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

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

• Talazoparib
• Tazemetostat

Conditions

Metastatic Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Keywords

Metastatic Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  Enrollment up to 28 days

• 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.

  Enrollment up to 2 years

Secondary Outcomes (1)

• Overall response rate (ORR)

  Enrollment up to 2 years

Study Arms (2)

Dose Escalation Talazoparib + Tazemetostat

EXPERIMENTAL

Standard 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.

Drug: Talazoparib; Drug: Tazemetostat

Dose Expansion Talazoparib + Tazemetostat

EXPERIMENTAL

Participants 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.

Drug: Talazoparib; Drug: Tazemetostat

Interventions

Talazoparib DRUG

capsule, taken by mouth, once a day

Also known as: Talzenna

Dose Escalation Talazoparib + Tazemetostat; Dose Expansion Talazoparib + Tazemetostat

Tazemetostat DRUG

orally as a tablet twice daily.

Also known as: Tazverik, EPZ-6438

Dose Escalation Talazoparib + Tazemetostat; Dose Expansion Talazoparib + Tazemetostat

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Epizyme, Inc.: collaborator
• Pfizer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

talazoparib; tazemetostat

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Atish Choudhury, MD PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 15, 2021
• Study Start: June 28, 2021
• Primary Completion: March 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)