A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)

Pfizer

Status and phase: Completed; Phase 3

Conditions: BRCA 1 Gene Mutation; BRCA 2 Gene Mutation; Breast Neoplasms

Treatments: Drug: Physician's-Choice; Drug: talazoparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01945775

C3441009 (Other Identifier)

2013-002716-28 (EudraCT Number)

673-301

U1111-1155-7579 (Other Identifier)

Details and patient eligibility

About

The purpose of this open-label, 2:1 randomized phase III trial is to compare the safety and efficacy of talazoparib (also known as BMN 673) versus protocol-specific physician's choice in patients who have locally advanced and/or metastatic breast cancer with germline BRCA mutations.

Enrollment: 431 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed carcinoma of the breast
• Locally advanced breast cancer that is not amenable to curative radiation or surgical cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy
• Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation from Myriad Genetics or other laboratory approved by the Sponsor
• No more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF)
• Prior treatment with a taxane and/or anthracycline in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated
• Have measurable or non-measurable, evaluable disease by the revised response evaluation criteria in solid tumors (RECIST) v.1.1
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion criteria

• First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy unless the Investigator determines that one of the 4 cytotoxic chemotherapy agents in the control arm would otherwise be offered to the subject

• Prior treatment with a PARP inhibitor (not including iniparib)

• Not a candidate for treatment with at least 1 of the treatments of protocol-specific physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)

• Subjects who had objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease; subjects who received low-dose platinum therapy administered in combination with radiation therapy are not excluded

• Subjects who have received platinum in the adjuvant or neoadjuvant setting are eligible; however, subjects may not have relapsed within 6 months of the last dose of prior platinum therapy

• Cytotoxic chemotherapy within 14 days before randomization

• Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days before randomization

• HER2 positive breast cancer

• Active inflammatory breast cancer

• CNS metastases

  • Exception: Adequately treated brain metastases documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of CNS symptoms. A repeat CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases.
  • Subjects with leptomeningeal carcinomatosis are not permitted

• Prior malignancy except for any of the following:

  • Prior BRCA-associated cancer as long as there is no current evidence of the cancer
  • Carcinoma in situ or non-melanoma skin cancer
  • A cancer diagnosed and definitively treated ≥ 5 years before randomization with no subsequent evidence of recurrence

• Known to be human immunodeficiency virus positive

• Known active hepatitis C virus, or known active hepatitis B virus

• Known hypersensitivity to any of the components of talazoparib

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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431 participants in 2 patient groups

talazoparib

Experimental group

Description:

Patient will be randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days

Treatment:

Drug: talazoparib

Physician's-Choice

Active Comparator group

Description:

Capecitabine, Eribulin, Gemcitabine or Vinorelbine

Treatment:

Drug: Physician's-Choice