Induction Therapy of PTX+BV Followed by Atezolizumab+Nab-PTX for PD-L1+ TNBC

Inclusion Criteria:

1. Diagnosed with metastatic recurrent or unresectable advanced TNBC

2. Documented PD-L1 positivity (SP142 IC ≥ 1) confirmed by local assessment of the mostrecent tumor sample or an archival tumor sample.

3. In the case of patients who were candidates for curative treatment, the durationfrom the completion of the curative treatment {date of surgery for primary breastcancer or date of last dose of peri-operative drug therapy (including anthracyclineregimen, taxane regimen, anti-PD-(L)1 antibody, capecitabine, poly ADP-ribosepolimerase [PARP] inhibitors, etc.), whichever is later} to the first local ordistant recurrence should be at least 6 months. The date of postoperativeradiotherapy is not included in this calculation. The use of anti-PD-(L)1 antibodiesis allowed during perioperative drug therapy.

4. ECOG PS 0-1

5. Female or male aged 18 years or older.

6. Histologically or cytologically confirmed TNBC that is ER-negative (< 10% positivecell occupancy or Allred Proportion score of 0-2), HER2-negative (IHC 1+ or less orFISH/DISH negative) according to ASCO/CAP Criteria 2018 (in the case of IHC2+,negativity is confirmed by FISH/DISH).

7. Patients who have not received chemotherapy for metastatic recurrent or unresectableadvanced cancer. However, prior treatment with PARP inhibitors for metastaticrecurrent or unresectable advanced cancers in patients with pathogenic BRCA variantsis allowed.

8. Having measurable or non-measurable lesions as assessed by local CT or MRI. Tumorlesions located at a previously irradiated site will be considered evaluable ifunequivocal progression is seen after radiation.

9. Laboratory tests performed within 14 days before enrollment meet the followingcriteria [1] to [8]. However, patients must not have received granulocytecolony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to thedate of blood sampling.

[1] Neutrophil count ≥ 1500/mm3 [2] Platelet count ≥ 10 x 104/mm3 [3] Hemoglobin ≥ 8.0 g/dL [4] AST (GOT) ≤ 100 IU/L (≤ 200 IU/L if liver metastasis is present) [5] ALT (GPT) ≤ 100 IU/L(≤ 200 IU/L if liver metastasis is present) [6] Total bilirubin ≤ 1.5 mg/dL Total bilirubin < 3.0 mg/dL for patients with Gilbert's syndrome [7] Creatinine ≤ 1.5 mg/dL [8] Any of the following criteria is met: i) Urine protein (dipstick) is negative (-) or 1+ ii) If urine protein (dipstick) is ≥ 2+; Measurement of 24-hour urine protein shows urine protein ≤ 1 g/24 hours (may be substituted by urine protein/creatinine ratio ≤ 1)

(10) Blood pressure is sufficiently controlled (systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg with ≤ 2 antihypertensive drugs [counted as the number of combinations]).

(11) Patients expected to survive for at least 3 months.

(12) Written consent has been obtained from the patient himself/herself after sufficient explanation of the contents of the study before registration.

(13) In the case of female patients of childbearing potential (including patients who have no menstruation for medical reasons such as chemical menopause), the patients must agree to continue to practice contraception until 5 months after the last dose of atezolizumab or 6 months after the last dose of bevacizumab, nab-PTX or PTX, whichever comes later. Patients must also agree not to breastfeed during study treatment and for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab. In the case of male patients with a partner of childbearing potential, the patient whose partner must agree to continue to practice contraception until 6 months after the last administration of PTX and nab-PTX.

Exclusion Criteria:

1. Having active brain metastases or carcinomatous meningitis. Previously treated brainmetastases are allowed if neurological symptoms have returned to baseline and areclinically stable for at least 2 weeks prior to enrollment.

2. Patients with a history of invasive malignancy within 3 years prior to enrollment.However, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, orlesions equivalent to carcinoma in situ or intramucosal carcinoma that are assessedas cured by local treatment are not included in active double cancer.

3. Concurrent or metachronous bilateral invasive breast cancer. However, the patientswill be accepted if bilateral lesions are TNBC and are confirmed to bePD-L1-positive by evaluation using a sample of a recurrent lesion.

4. Patients who have received radiotherapy within 14 days prior to enrollment. (Administration or irradiation on the same day of the week 14 days prior to the dayof enrollment is permitted.)

5. Patients who have received other study drugs within 14 days prior to enrollment. (Administration on the same day of the week 14 days prior to the day of enrollmentis permitted.)

6. Administration of a live vaccine within 30 days of the first dose of the study drug.Administration of inactivated vaccines is permitted.

7. Patients who have received systemic corticosteroid or immunosuppressant equivalentto prednisone exceeding 10 mg/day within 14 days prior to enrollment for activeautoimmune disease. (excluding temporary administration for examination orprophylactic administration)

8. Active infection requiring systemic treatment.

9. Patients who concurrently have interstitial lung disease/pneumonitis at the time ofenrollment or who have a history of interstitial lung disease/pneumonitis requiringsystemic corticosteroids administration. (A history of radiation pneumonitis [fibrosis] within the radiation field is permitted.)

10. Patients who are pregnant, possibly pregnant, or lactating.

11. Patients who are positive for HBs antigen or HCV antibody. Patients positive for HCVantibody whose HCV virus level is below the detection limit will be permitted.

12. Patients who are positive for HIV-1 antibody or HIV-2 antibody (test is notessential for enrollment).

13. Patients with significant cardiovascular disease. Patients with a history ofmyocardial infarction, acute coronary artery disease, coronaryangioplasty/stenting/bypass grafting within the last 6 months. Patients withcongestive heart failure of Class III to IV of the New York Heart Association.

14. Patients with the following history/concomitant diseases:

[1] Poorly controlled diabetes mellitus [2] Grade ≥ 2 peripheral sensory neuropathy [3] Congenital haemorrhagic diathesis/coagulopathy [4] Arterial thromboembolism (cerebral infarction, etc.) or venous thromboembolism (deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to enrollment [5] Gastrointestinal perforation, active gastrointestinal ulcer, and Grade ≥ 3 haemorrhage (site not specified) [6] Other serious complications (renal failure, hepatic failure, etc.)

(15) Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's completion of the study, or is not in the best interest of the participant to participate in.

(16) Patients with any psychiatric condition that may interfere with the conduct of the study.

(17) Patients with a history of hypersensitivity to the study drug or its analogues.

(18) Patients with alcohol intolerance or a history of hypersensitivity to Cremophor.

(19) Patients with a history of active tuberculosis infection.