Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Patients With Previously Untreated Metastatic Triple-Negative Breast Cancer
Brief Summary: This multicenter, randomized, double-blind study evaluated the efficacy, safety, and pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with placebo in combination with nab-paclitaxel in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic breast cancer (mBC). The safety of single-agent nab-paclitaxel has been determined in previous studies of participants with mBC and the safety data to date suggest that atezolizumab can be safely combined with standard chemotherapy agents.


Options:
A: Inclusion Criteria:

* Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
* No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
* Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
* A representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks, or at least 20 unstained slides with an associated pathology report documenting ER, PR, and HER2 negativity. Participants with fewer than 20 unstained slides available at baseline, and not fewer than 12 unstained slides will be eligible upon discussion with Medical Monitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end-organ function

Exclusion Criteria:

* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Pregnancy or lactation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization, during treatment, or within 5 months following the last dose of atezolizumab/placebo
B: Inclusion Criteria:

* Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
* Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
* Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
* If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
* Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
* Subject must have adequate bone marrow, renal and hepatic function.
* Subject must not be pregnant or plan to conceive a child.

Exclusion Criteria:

* Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1.
* More than 2 prior lines of cytotoxic chemotherapy.
* Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
* Prior taxane therapy for metastatic breast cancer.
* A history of or evidence of brain metastases or leptomeningeal disease.
* A history of uncontrolled seizure disorder.
* Pre-existing neuropathy from any cause in excess of Grade 1.
* Known history of allergic reaction to cremophor/paclitaxel.
* Clinical significant uncontrolled conditions, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
* Pregnant or breastfeeding.
C: Inclusion Criteria:

- Histologically documented breast cancer (either primary or metastatic site) that is ER-negative, PR-negative, and HER2 non-overexpressing by immunohistochemistry (0, 1) or fluorescence in situ hybridization (FISH).

Triple-negative tumors were defined by the following criteria:

* HER2-non-overexpressing: FISH-negative (defined by ratio \<2.2) or, immunohistochemical (IHC) 0, IHC 1+ or, IHC 2+ or IHC 3+ and FISH-negative.
* ER- and PR-negative: \<10% tumor staining by immunohistochemistry (IHC).

  * Never having received chemotherapy for metastatic disease or, having received 1 or 2 prior chemotherapy regimens in the metastatic setting (Prior adjuvant/neoadjuvant therapy was allowed);
  * Metastatic breast cancer (Stage IV) with measurable disease by RECIST 1.1 criteria;
  * Female, ≥18 years of age;
  * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
  * Organ and marrow function as follows: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/dL, hemoglobin ≥9 g/dL, bilirubin ≤1.5 mg/dL, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement;
  * Radiation therapy completed at least 14 days before study dosing on day 1; radiated lesions may not have served as measurable disease;
  * Central nervous system metastases allowed if subject did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
  * For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy;
  * Tissue block (primary or metastatic) or readily available fresh frozen tumor tissue for PARP expression and other pharmacogenomic studies recommended (although its absence will not exclude subjects from participating);
  * No other diagnosis of malignancy (with exception of non melanoma skin cancer or a malignancy diagnosed ≥5 years ago);
  * Obtained informed consent;
  * Capability to understand and comply with the protocol and signed informed consent document.

Exclusion Criteria:

* Systemic anticancer therapy within 14 days of the first dose of study drug;
* Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib
* Had not recovered to grade ≤1 from adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 or to within 10% of baseline values due to investigational drugs or other medications administered more than 30 days prior to study enrollment;
* Major medical conditions that might have affected study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);
* Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation was acceptable;
* Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;
* Pregnancy or breastfeeding;
* Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
D: Inclusion Criteria:

* Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
* Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
* Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
* Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed.
* ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
* ECOG performance status 0-1.
* Adequate bone marrow, kidney and liver function.

Exclusion Criteria:

* Prior treatment with PARP inhibitor.
* Patients with HER2 positive disease.
* More than 2 prior lines of chemotherapy for metastatic breast cancer.
* Untreated and/or uncontrolled brain metastases.
* Prior malignancy unless curatively treated and disease-free for \> 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed.
* Known HIV (Human Immunodeficiency Virus) infection.
* Pregnant or breast-feeding women.

Answer: A