A Study to Evaluate TAlazoparib, Radiotherapy and Atezolizumab in gBRCA 1/2 Negative Patients With PD-L1+ Metastatic Triple Negative Breast Cancer

NCT04690855 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN BRE19-433
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase II study designed to assess efficacy and safety of talazoparib, high dose radiation, and atezolizumab in patients with metastatic TNBC that is PD-L1 positive. A total of 23 gBRCA pathogenic variant negative patients will be enrolled. All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1. Patients will then receive 8 Gy x 3 fractions to 2-4 metastatic lesions beginning Day 12,13, or 14 and given QOD. 840 mg of atezolizumab will be given intravenously (IV) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the remaining cycles. The sequence of administration is not specified on the days in which talazoparib and atezolizumab are given on the same day. Each cycle equals 28 days. Treatment will continue until progression or severe toxicity. A safety lead in of up to 6 patients will be performed. Immune-related and non-immune related adverse events will be tracked up to 12 weeks post initiation of atezolizumab, as the majority of treatment-related toxicities from talazoparib, radiation, and atezolizumab occur within this time period.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) by RECIST 1.1

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence

  Up to a maximum of 5 months

Secondary Outcomes (8)

• Assess Adverse Events

  Up to a maximum of 12 months.

• Progression Free Survival (PFS)

  Time of treatment start until the criteria for disease progression or death, up to a maximum of 5 months.

• Overall Survival (OS)

  Time of treatment start until death, up to a maximum of 12 months.

• ORR by Immune-related RECIST (irRECIST)

  Up to a maximum of 5 months

• Duration of Overall Response (DOR)

  Up to a maximum of 5 months

Study Arms (1)

Study Treatment Arm

EXPERIMENTAL

All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1. Patients will then receive 8 Gy x 3 fractions to 1-4 metastatic lesions beginning Day 12,13, or 14 and given QOD. 840 mg of atezolizumab will be given intravenously (IV) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the remaining cycles. The sequence of administration is not specified on the days in which talazoparib and atezolizumab are given on the same day. Each cycle equals 28 days. Treatment will continue until progression or severe toxicity. A safety lead in of up to 6 patients will be performed. Immune-related and non-immune related adverse events will be tracked up to 12 weeks post initiation of atezolizumab, as the majority of treatment-related toxicities from talazoparib, radiation, and atezolizumab occur within this time period.

Drug: Talazoparib; Drug: Atezolizumab; Radiation: Radiation

Interventions

Talazoparib DRUG

Talazoparib 1 mg Orally Day 1 to Day 28

Also known as: Talzenna

Study Treatment Arm

Atezolizumab DRUG

Atezolizumab 840 mg IV over 60 minutes Day 15 of Cycle 1 then Day 1 and Day 15 of subsequent Cycles

Also known as: Tecentriq

Study Treatment Arm

Radiation RADIATION

Radiation 8 Gy will be given in 3 fractions QOD beginning Day 12, 13 or 14 of Cycle 1 but 24-72 hours prior to 1st dose of Atezolizumab

Study Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent and HIPPA for the trial.
• Ages 18-75 years old at time of consent. Female or male patients allowed.
• ECOG PS of 0-2, KPS \>/= 60%.
• Biopsy proven metastatic triple negative breast cancer (estrogen receptor (\</=10%), progesterone receptor (\</=10%) and no overexpression of HER2 as evaluated by local institutions with at least 2 exracranial lesions of metastatic disease on imaging.
• PD-L1 positive tumor infiltrate as defined as \>/= 1% on IHC using the SP142 Ventana Assay.
• Known gBRCA 1/2 status (gBRCA 1/2 negative \[e.g. gBRCA wild-type, gBRCA variants of uncertain significance\] are eligible).
• Patients must have at least 1 extracranial metastatic lesion (may be measurable or non-measurable disease by RECIST v 1.1) that is amenable to high dose radiotherapy and at least one additional extracranial lesion of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) that will not receive radiotherapy on this study. Of note, lesions maybe in the same organ but must be 2 cm apart and breast lesions may be treated.
• Patients must have received at least one and no more than three previous lines of systemic treatment in the advanced setting with or without immune therapy. Patients with disease recurrence or progression following neoadjuvant or adjuvant cytotoxic chemotherapy are not eligible unless they have received at least one line of chemotherapy with or without immune therapy in the advanced setting. NOTE: Targeted small molecules (e.g. tyrosine kinase inhibitors), hormonal agents and monoclonal antibodies that inhibit angiogenesis (e.g. bevacizumab, afilbercept) are not counted in the number of lines of therapy. Cytotoxic chemotherapy with or without immune therapy for advanced disease prior to protocol treatment is not permitted within 2 weeks of the protocol treatment. Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study 2 weeks after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) for mTNBC and have sufficient resolution of side effects per physician assessment at time of talazoparib.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
• Absolute neutrophil count \> 1500/mcL
• Platelets \>/= 100,000 mm
• Anemia \>/= 9.0 g/dL (NOTE: The use of transfusion or other intervention to achieve Hgb \>/= 9.0g/dl is acceptable)
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels \> 1.5× institutional ULN
• Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5×ULN

You may not qualify if:

• gBRCA1/2 pathogenic variant positive
• Four or more lines of cytotoxic chemotherapy for mTNBC.
• Previous radiation to the metastases to be treated with radiation on this protocol.
• Previous PARPi treatment (e.g. talazoparib, niraparib, olazaparib).
• Progression of breast cancer within the first 3 months of prior immune therapy for non-metastatic or metastatic breast cancer.
• Untreated CNS disease (patients with stable CNS disease for at least 28 days and asymptomatic treated CNS metastases are permitted).
• History of leptomeningeal disease.
• History of autoimmune disease that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Use of systemic glucocorticoid or immunosuppressive medications at time of enrollment.
• Severe, active co-morbidity such as CHF or unstable angina within last 6 months, transmural MI within the last 6 months.
• Acute bacterial or fungal infection requiring IV antibiotics at time of registration.
• COPD or other respiratory illness requiring hospitalization at time of registration.
• HIV positive with CD4 count \<200 cells/ microliter.
• Current hormone replacement therapy use.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Indolent cancers (such as low risk prostate or in-situ cancers) that are not being treated, are acceptable.

Sponsors & Collaborators

• Mylin A. Torres, MD: lead
• Genentech, Inc.: collaborator
• Pfizer: collaborator
• Emory University: collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

talazoparib; atezolizumab; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

(317) 921-2050

Study Officials

• Mylin Torres, MD

  Winship Cancer Institute, Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: December 31, 2020
• Study Start: October 4, 2021
• Primary Completion: February 18, 2022
• Study Completion: December 20, 2022
• Last Updated: December 4, 2023
• Results First Posted: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)