TALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer

NCT03964532 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00000023
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-institutional pilot trial for patients with advanced breast cancer. The trial is designed to assess the safety and tolerability of induction talazoparib followed by combination of talazoparib and avelumab. As an exploratory endpoint, the study team will evaluate the immunomodulatory effects of induction talazoparib followed by the combination of talazoparib and avelumab in patients with advanced breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer; Advanced Breast Cancer; Talazoparib; Avelumab

Outcome Measures

Primary Outcomes (1)

• Quantification of Grade 3 and 4 toxicities (Adverse Events)

  Quantification of grade 3 and 4 toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 \[NCI CTCAE v4.03\]. Toxicity analysis will be conducted in all patients receiving at least one dose of talazoparib.

  from the start of study drugs through 30 days after end of treatment (approximately 1 year)

Secondary Outcomes (1)

• The anti-tumor efficacy as measured by Objective Response Rate (ORR).

  4 Months

Other Outcomes (4)

• The anti-tumor efficacy as measured by Progression Free Survival (PFS).

  Up to 5 years

• The anti-tumor efficacy as measured by Overall Survival (OS).

  Up to 5 years

• The anti-tumor efficacy as measured by Duration of Response (DOR).

  Up to 5 years

Study Arms (1)

Phase I/Phase II

EXPERIMENTAL

Talazoparib (1mg by mouth \[PO\] daily D1-28) will be provided as monotherapy for the first cycle. Starting with cycle 2 and for all subsequent cycles, treatment with avelumab (800 mg intravenously \[IV\] D1 every 2 weeks) will be added to talazoparib.

Drug: Talazoparib; Drug: Avelumab

Interventions

Talazoparib DRUG

Talazoparib (formerly MDV3800 and BMN673) is an oral small molecule, selective inhibitor of PARP-1 and PARP-2.

Also known as: Talzenna

Phase I/Phase II

Avelumab DRUG

Avelumab (formerly MSB0010718C) is a human immunoglobulin G1 (IgG1) anti-PD-L1 monoclonal antibody131 that utilizes both adaptive and innate immune mechanisms.

Also known as: Bavencio

Phase I/Phase II

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, that is amenable to biopsy
• Radiographically measurable disease by RECIST v1.1
• Age ≥ 18 years
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Signed informed consent form
• Patients with a standard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):
• QTc interval at screening \< 481 msec
• Resting heart rate 50-100bpm
• Adequate hepatic, bone marrow, and renal function at the time of enrollment:
• Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL. Patients must be able to meet the criteria without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample
• Creatinine clearance ≥ 60 mL/min based on Cockcroft-Gault equation
• Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × the upper normal limit of institution's normal range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range, except for subjects with documented history of Gilbert's syndrome who may enroll at Investigator discretion. For subjects with liver metastases, AST and ALT \< 5 × the upper normal limit of institution's normal range, and total bilirubin \>1.5 - 3.0 x the upper normal limit of institution's normal range are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia
• Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must be ≤ 2 X the upper limit of the institution's normal range and International Normalized Ratio (INR) \< 2. Subjects on anticoagulation (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator
• Patients may have received an unlimited number of prior therapies. The last dose of systemic therapy must have occurred a minimum of 2 weeks prior to C1D1.

You may not qualify if:

• Prior disease progression while receiving anti-PD-1 or anti-PD-L1 therapy within 6 months of use
• Prior exposure to PARP inhibitor-based therapy
• Patients with known untreated central nervous system (CNS) metastases
• Recent severe infection or antibiotic use, or known chronic infection with human immunodeficiency virus (HIV) or hepatitis B virus
• Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
• Diagnosis of immunodeficiency or is receiving systemic steroid or other immunosuppressive therapy
• Active autoimmune disease that has required systemic treatment in the past 2 years
• History of tuberculosis
• History of allogenic bone marrow transplant or solid organ transplant
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
• Life-threatening visceral disease or other severe concurrent disease that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol
• Live vaccine administration within 30 days of planned start of study therapy
• Cardiovascular disease problems including unstable angina, therapy for lifethreatening ventricular arrhythmia, or myocardial infarction, stroke within the last 6 months, or a diagnosis of congestive heart failure
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
• Presence of a psychiatric illness or social situation that would limit compliance with study requirements

Sponsors & Collaborators

• Georgetown University: lead
• Pfizer: collaborator

Study Sites (2)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

talazoparib; avelumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Claudine Isaacs, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: May 28, 2019
• Study Start: April 17, 2019
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (2)