Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors

NCT02401347 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-31913NCI-2015-00036BRS0050
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this single-arm phase 2 clinical trial is to evaluate the anti-cancer activity of Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative breast cancer are eligible.

Conditions

Advanced Breast Cancer; HER2/Neu Negative; Triple-Negative Breast Cancer

Keywords

PALB2 mutation; BRIP1 mutation; BARD1 mutation; Rad51c mutation; PTEN mutation; CHEK2 mutation; ATM mutation; NBN mutation; Rad51d mutation; Rad50 mutation; MRE11 mutation; FANC mutation; HRD assay score; ATR mutation

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR)

  Objective response (OR) is a common measure of benefit. OR is defined as the number of participants who achieved complete response (CR) or partial clinical (PR), per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (v1.1). RECIST Criteria are assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays, as follows: * CR = Disappearance of all target and non-target lesions * PR = ≥30% decrease in the sum of the long diameter of target lesions * OR = CR+PR * Stable disease (SD) = Small changes that do not meet any of the above criteria * Progressive disease (PD) = ≥20% increase in long diameter of target lesions, and/or the appearance of any new lesion(s) The outcome is expressed as the number of participants that achieved either CR or PR within 24 weeks of the start of treatment, a number without dispersion.

  up to 24 weeks

Secondary Outcomes (2)

• Clinical Benefit (CB)

  up to 24 weeks

• Progression-free Survival (PFS)

  1 year

Study Arms (2)

Cohort A - Triple-negative Breast Cancer

EXPERIMENTAL

Participants with advanced triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD) based on the Myriad HRD Assay. Participants receive talazoparib 1 mg by mouth daily.

Drug: Talazoparib Tosylate

Cohort B - HER2-negative solid tumor

EXPERIMENTAL

Participants with advanced HER2-negative solid tumor with a deleterious hereditary or cancer somatic mutation in one of the following genes: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes. Participants receive talazoparib 1 mg by mouth daily.

Drug: Talazoparib Tosylate

Interventions

Talazoparib Tosylate DRUG

Participants receive Talazoparib tosylate at 1 mg by mouth daily.

Also known as: BMN 673

Cohort A - Triple-negative Breast Cancer; Cohort B - HER2-negative solid tumor

Eligibility Criteria

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

You may qualify if:

• No deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and comprehensive rearrangement testing at an external reference laboratory; patients with variants of unknown significance will be eligible
• Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
• Must have progressed on at least 1 prior chemotherapy regimen for the treatment of advanced breast cancer; there is no upper limit on the number of prior therapies
• If prior platinum agent (eg, carboplatin or cisplatin) has been administered, no evidence of progression, or within 8 weeks of stopping platinum treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤ 5 x ULN
• Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for Gilbert's syndrome)
• Calculated creatinine clearance ≥ 30 mL/min or serum creatinine ≤ 1.5 mg/dL
• Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before day 1 of study drug
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Able to take oral medications
• Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Sexually active patients of childbearing potential must be willing to use an acceptable method of contraception such as an intrauterine device or double barrier contraception during treatment and for 30 days after the last dose of study drug
• Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study; females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy

You may not qualify if:

• Any patient with a deleterious mutation in BRCA1 or BRCA2
• Hormone receptor positive and/or HER2 positive breast cancer (Cohort A only)
• HER2 positive breast cancer (Cohort B only)
• Prior treatment with a PARP inhibitor
• Non-measurable disease only
• Pregnant or nursing patients
• Any anti-cancer therapy within the past 21 days of the first day of treatment
• Brain or central nervous system (CNS) metastases
• Exception: Adequately treated brain metastases documented by baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan that have not progressed since previous scans and do not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of CNS symptoms. A repeated 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
• Other malignancy that is either active or for which patient has received treatment in the last five years excluding non-melanoma skin cancer and carcinoma in situ of the cervix
• Radiation therapy in the last 14 days
• Known to be human immunodeficiency virus positive
• Known active hepatitis C virus
• Known active hepatitis B virus

Sponsors & Collaborators

• Melinda Telli: lead
• BioMarin Pharmaceutical: collaborator
• Pfizer: collaborator

Study Sites (1)

Stanford Medicine at Stanford University

Stanford, California, 94305, United States

Location

Related Publications (1)

• Gruber JJ, Afghahi A, Timms K, DeWees A, Gross W, Aushev VN, Wu HT, Balcioglu M, Sethi H, Scott D, Foran J, McMillan A, Ford JM, Telli ML. A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes. Nat Cancer. 2022 Oct;3(10):1181-1191. doi: 10.1038/s43018-022-00439-1. Epub 2022 Oct 17.

  PMID: 36253484 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Melinda L Telli, MD
• Organization: Stanford Medicine at Stanford University

mtelli@stanford.edu

(650) 724-9533

Study Officials

• Melinda L Telli, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: March 27, 2015
• Study Start: August 1, 2015
• Primary Completion: December 23, 2019
• Study Completion: December 1, 2022
• Last Updated: February 21, 2023
• Results First Posted: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)