Phase 3 Randomized Study of Talazoparib with Enzalutamide in Men with DDR Gene Mutated mCSPC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Sep 2021 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-510809-28-00

EudraCT number

2021-000248-23

ClinicalTrials.gov

NCT04821622

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacogenomic, Pharmacodynamic, Safety, Therapy

To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging investigator-assessed Radiographic Progression-free Survival (rPFS), in participants with mCSPC harboring HRR deficiencies.

Secondary objectives 1

1. To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging overall survival (OS) in participants with mCSPC harboring HRR deficiencies

Conditions and MedDRA coding

Metastatic Castration-sensitive Prostate Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell or signet cell features
2. 2. Confirmation of DDR gene mutation status by prospective or historical analysis (with sponsor pre-approval) of blood (liquid biopsy) and/or de novo or archival tumor tissue using FoundationOne® Liquid CDx or FoundationOne® CDx
3. 3. Ongoing ADT with a gonadotropin-releasing hormone (GnRH) agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated before randomization and must continue throughout the study
4. 4. Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on CT or MRI scan (for soft tissue). Participants whose disease spread is limited to regional pelvic lymph nodes are not eligible. Note: a finding of superscan at baseline is exclusionary
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Exclusion criteria 6

1. 1. Other acute or chronic medical [concurrent disease, infection, including chronic stable Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, or co-morbidity] or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that interferes with a participant’s ability to participate in the study, may increase the risk associated with study participation or study treatment administration, or may interfere with the interpretation of study results, and, in the investigator’s judgment, make the participant inappropriate for entry into the study. HIV/HBV/HCV testing is not required unless mandated by local health authority.
2. 2. History of seizure or any condition (as assessed by investigator) that may predispose to seizure
3. 3. Known or suspected brain metastasis or active leptomeningeal disease.
4. 4. Clinically significant cardiovascular disease.
5. 5. Prior treatment in any setting with NHT except prior ADT in the adjuvant/neoadjuvant setting, where the completion of ADT was less than 12 months prior to randomization and the total duration of ADT exceeded 36 months.
6. 6. Any previous treatment with DNA-damaging cytotoxic chemotherapy (ie, platinum based therapy) within 5 years prior to randomization, except for indications other than prostate cancer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Investigator-assessed rPFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1 [soft tissue disease]) and Prostate Cancer Working Group (PCWG3 [bone disease]) in participants with mCSPC harboring HRR deficiencies.

Secondary endpoints 1

1. OS in participants with mCSPC harboring HRR deficiencies (alpha protected).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 5

Locations

12 EU/EEA countries · 69 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 95 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications