A Study of Neoadjuvant Nivolumab + Palbociclib + Anastrozole in Post-Menopausal Women and Men With Primary Breast Cancer

RCB 0-I rate is defined as the percentage of randomized participants who achieve RCB 0: no residual disease or RCB-I: minimal residual disease. RCB is a continuous index combining pathological measurements of primary tumor (size and cellularity) and nodal metastases (number and size) defined by a point system at surgery. No participants continued to the randomized phase; trial was closed after completion of the Safety Run-in.

Time frame: From randomization phase up to 5 treatment cycles (up to approximately 20 weeks)

Population: All randomized participants in the Randomized phase.

The number of participants with dose limiting toxicities (DLTs) during the safety run-in phase. DLTS are defined as treatment emergent adverse events (TEAE) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 that occurs during the first 4 weeks (1 cycle) after treatment. Participants who withdraw from the study during the DLT evaluation period or have received less than 1 dose of nivolumab and 75% of accumulative doses of palbociclib of the cycle for reasons other than a DLT will not be considered as DLT-evaluable participants.

Time frame: From first dose to 4 weeks after first dose

Population: All DLT-evaluable participants

The percentage of participants who undergo breast conserving surgery (BCS) after completing the study treatments. Confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to approximately 6 months after first dose

Population: All Treated Participants in the Safety Run-In Phase

ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per investigator radiographic assessment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From first dose up to approximately 6 months after first dose

Population: All Treated Participants in the Safety Run-in Phase

The percentage of participants with an absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to approximately 6 months after first dose

Population: All Treated Participants in the Safety Run-In Phase

The number of participants that have died during the study.

Time frame: From first dose up to approximately 8 months

Population: All Treated Participants in the Safety Run-In Phase

The number of participants experiencing adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Population: All Treated Participants in the Safety Run-In Phase

The number of participants experiencing adverse events (AEs) that lead to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Population: All Treated Participants in the Safety Run-In Phase

The number of participants experiencing adverse events that are immune-related. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 8 months)

Population: All DLT-evaluable participants in the Safety Run-in Phase

The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal

Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Population: All Treated Participants in the Safety Run-in Phase

The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal

Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Population: All Treated Subjects in Safety Run-in Phase with at Least One On-Treatment TSH measurement

The number of participants experiencing serious adverse events (SAEs). A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Population: All Treated Participants in the Safety Run-In Phase