PALbociclib Endocrine Therapy Followed by Talazo Vs. Talazoz-Atezo Study

NCT ID: NCT04819243

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-25
• Study Completion Date: 2027-12-31

Brief Summary

This study is a prospective, two-arm, randomized phase II study of talazoparib versus talazoparib plus atezolizumab in ER+ premeonopausal women with metastatic breast cancer harboring HRD scar

1st line treatment: GnRH agonist + Aromatase Inhibitor(AI) + Palbociclib 28 days after the last treatment of 1st line treatment(., randomization for 2nd line treatment is conducte to arm A(Talazoparib+Atezolizumab) and arm B(Talazoparib monotherapy)

Detailed Description

1. st line treatment

• Palbociclib: A capsule will be administered once a day for 21 days and rest for 7 days (1cycle=28days)
• AI treatment: D1~28 days. Take once a day. Prescribed according to local prescribe guideline.
• GnRH agonist: At D1 for every cycle with 4 week (+3days) interval via subcutaneous injection.

(or ET + CDK4/6 inhibitors + GnRH agonist)

2. nd line treatment

28 days after the last treatment of 1st line treatment, randomization for 2nd line treatment is conducte to arm A(Talazoparib+Atezolizumab) and arm B(Talazoparib monotherapy)

• Talazoparib: Take orally once a day at the same time
• Atezolizumab: 1,200mg, at D1 of each cycle. Applicable for arm A only.

Conditions

Premenopausal HR+/HER2- Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab+Talazoparib

1. st line treatment

• Palbociclib 125mg po D1-21
• AI : Prescribed as per local guideline
• GnRH agonist: Prescribed as per local guideline (or ET + CDK4/6 inhibitors + GnRH agonist)

2. nd line treatment

• Talazoparib 1mg po
• Atezolizumab 1200mg IV (3week)

Group Type: EXPERIMENTAL

Pabociclib, Endocrine(or ET + CDK4/6 inhibitors), Talazoparib, Atezolizumab

Intervention Type: DRUG

• Palbociclib 125mg
• AI
• GnRH agonist (or ET + CDK4/6 inhibitors + GnRH agonist)
• Talazoparib
• Atezolizumab

Talazoparib

1. st line treatment

• Palbociclib 125mg po D1-21
• AI : Prescribed as per local guideline
• GnRH agonist: Prescribed as per local guideline (or ET + CDK4/6 inhibitors + GnRH agonist)

2. nd line treatment - Talazoparib 1mg po

Group Type: EXPERIMENTAL

Pabociclib, Endocrine(or ET + CDK4/6 inhibitors), Talazoparib,

Intervention Type: DRUG

• Palbociclib 125mg
• AI
• GnRH agonist (or ET + CDK4/6 inhibitors + GnRH agonist)
• Talazoparib

Interventions

Pabociclib, Endocrine(or ET + CDK4/6 inhibitors), Talazoparib, Atezolizumab

• Palbociclib 125mg
• AI
• GnRH agonist (or ET + CDK4/6 inhibitors + GnRH agonist)
• Talazoparib
• Atezolizumab

Intervention Type: DRUG

Pabociclib, Endocrine(or ET + CDK4/6 inhibitors), Talazoparib,

• Palbociclib 125mg
• AI
• GnRH agonist (or ET + CDK4/6 inhibitors + GnRH agonist)
• Talazoparib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

3. Confirmed germline pathogenic BRCA1 and/or 2 mutation or 35 HRD-related gene alterations (see Appendix 16.5)

4. age > 19 years

5. ECOG performance status 0 - 2

6. Patient has HER2 IHC0, IHC1+, or ICH2+/ISH-, as determined according to ASCO/CAP guidelines breast cancer

7. Patient has ER positive and/or PgR positive according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as 1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally

8. Female patients should be premenopausal. Premenopausal status is defined as either:

A. Patient had last menstrual period within the last 12 months B. If on tamoxifen within the past 3 months, with a plasma estradiol ≥10 pg/mL and FSH ≤40 IU/l or in the premenopausal range, according to local laboratory definition C. in case of chemotherapy induced amenorrhea, with a plasma estradiol ≥10 pg/mL) and/or FSH ≤40IU/l or in the premenopausal range according to local laboratory definition.

9. Patient with treatment history as bellows:

A. In patients with de novo metastatic breast cancer(who had stage IV disease at first diagnosis of breast cancer), B. In patients with recurrent metastatic breast cancer, recurrence during or after completion or discontinuation of adjuvant endocrine therapy (regardless of the treatment free interval) are eligible.

C. One line of prior cytotoxic chemotherapy(except platinum based chemotherapy) in metastatic breast cancer is permitted.

10. No possibility of pregnancy and/or urine or serum beta-HCG negative

11. Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)

12. Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 60 ml/min)

13. Adequate liver function (≤ serum bilirubin 2.0 mg/dl, ≤ AST/ALT x 3 upper normal limit). If the subject has liver metastasis, AST/ALT x 5 upper normal limit is acceptable.

14. Patients who were already established on bisphosphonate therapy or denosumab may continue.

15. Patients agreed to use effective contraception or not of childbearing potential

16. Written informed consent

17. Patients agreed to offer tumor tissue and blood for biomarker analysis

1. ECOG performance status 0 - 2

2. Adequate bone marrow function (≥ANC 1,500/ul, ≥platelet 100,000/ul, ≥Hemoglobin 9.0 g/dl)

3. Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 60 ml/min)

4. Adequate liver function (≤ serum bilirubin 2.0 mg/dl, ≤ AST/ALT x 3 upper normal limit) If the subject has liver metastasis, AST/ALT x 5 upper normal limit is acceptable

5. Histologically confirmed metastatic or locally advanced breast cancer that is not amenable to curative surgery, with or without measurable disease. Patients who have stage IV breast cancer at diagnosis (de novo) or have progressed on distant metastatic sites after curative surgery are eligible.

6. Prior treatment with endocrine-based therapy + CDK4/6 inhibitor for metastatic or inoperable locally advanced breast cancer. Allowed endocrine-based therapy is as below:

A. Aromatase Inhibitor B. For subjects who had disease progression during or after the adjuvant aromatase inhibitor therapy, fulvestrant C. Up to one line of chemotherapy for metastatic or inoperable locally advanced breast cancer is allowed except for platinum based chemotherapy.

7. Confirmed germline pathogenic BRCA1 and/or BRCA2 mutation or 35 HRD-related gene alterations (see Appendix 16.5)

8. age > 19 years

9. Patient has HER2 IHC0, IHC1+, or ICH2+/ISH-, as determined according to ASCO/CAP guidelines breast cancer

10. Patient has ER positive and/or PgR positive according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as 1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally

11. Female patients should be premenopausal. Premenopausal status is defined as either:

A. Patient had last menstrual period within the last 12 months B. If on tamoxifen within the past 3 months, with a plasma estradiol ≥10 pg/mL and FSH ≤40 IU/l or in the premenopausal range, according to local laboratory definition C. in case of chemotherapy induced amenorrhea, with a plasma estradiol ≥10 pg/mL) and/or FSH ≤40IU/l or in the premenopausal range according to local laboratory definition.

D. If the subject started ovarian function suppression, above A-C criteria should be met prior to starting ovarian function suppression.

12. No possibility of pregnancy and/or urine or serum beta-HCG negative

13. Patients may continue an ongoing bisphosphonate or denosumab therapy.

14. Patients who agreed to use an effective contraception method or have no childbearing potential

15. Written informed consent

16. Patients who agreed to offer tumor tissue and blood for biomarker analysis

Exclusion Criteria

1. Postmenopausal women except women who had BSO (Bilateral Salpingo Oophorectomy)

2. Serious uncontrolled intercurrent infections within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment

3. Serious intercurrent medical or psychiatric illness, including active cardiac disease

4. Participants who are pregnant or breast feeding or intending to become pregnant during the study or within 5 months after the final dose of study treatments.

5. Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or favorable thyroid papillary carcinoma(follicular thyroid cancer, including PTC) or other malignancy treated at least 5 years previously with no evidence of recurrence)

6. Patients has received previous endocrine treatments in the metastatic setting (Except tamoxifen only ± GnRH agonist)

7. Patients has received previous aromatase inhibitor (less than 1 year after the last dose)

8. Patients has received previous treatment with CDK 4/6 inhibitors, OR PARP1 inhibitors, OR immune check point inhibitors (less than 1 year after the last dose)

9. Known brain metastases, symptomatic or asymptomatic

10. History of clinically significant liver disease, current alcohol abuse or known active infection

11. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

12. Prior allogeneic stem cell or solid organ transplantation

13. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan

14. Active tuberculosis

15. Receipt of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment or anticipation that a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months after the last dose of atezolizumab

16. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interlukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to Cycle 1 Day 1 of 1st Treatment

17. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, mycophenolate, and anti-tumour necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1 Day 1 of 1st Treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

1. Postmenopausal women except women who had BSO (Bilateral Salpingo Oophorectomy)

2. Serious intercurrent medical or psychiatric illness, including active cardiac disease

3. Participants who are pregnant or breast feeding or intending to become pregnant during the study or within 5 months after the final dose of study treatments.

4. Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or favorable thyroid papillary carcinoma(follicular thyroid cancer, including PTC) or other malignancy treated at least 5 years previously with no evidence of recurrence)

5. Patients who have previously received PARP1 inhibitors OR immune check point inhibitors

6. Patients who have previously received platinum based chemotherapy or two or more lines of chemotherapy for metastatic or inoperable locally advanced breast cancer

7. Known brain metastases, symptomatic or asymptomatic

8. History of clinically significant liver disease, current alcohol abuse or known active infection

9. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

10. Prior allogeneic stem cell or solid organ transplantation

11. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan

12. Active tuberculosis

13. Receipt of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment or anticipation that a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months after the last dose of atezolizumab

14. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interlukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to Cycle 1 Day 1 of 1st Treatment

15. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, mycophenolate, and anti-tumour necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1 Day 1 of 1st Treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Yeon Hee Park

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Samsung medical Center

Seoul, Gannam-gu, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Yeon Hee Park, phD

Role: CONTACT

yeonh.park@samsung.com

+82-2-3410-1780

mieun Kim, CRA

Role: CONTACT

mieun2728.kim@samsung.com

+82 2-2148-7664

Facility Contacts

Yeon Hee Park, phD

Role: primary

yeonh.park@samsung.com

82-2-3410-1780

mieun Kim, CRA

Role: backup

mieun2728.kim@samsung.com

82-2-2148-7664

Yeon Hee Park, phD

Role: backup

Other Identifiers

2021-01-075

Identifier Type: -

Identifier Source: org_study_id