A Study of a Medicine Called Atirmociclib in Combination With Giredestrant in Adult Participants With ER-positive, HER2-negative Early-stage Breast Cancer

• Atirmociclib (Drug), also known as PF-07220060: Atirmociclib tablet given orally twice daily, plus giredestrant capsule given orally once per day
• giredestrant (Drug): giredestrant capsule given once a day
• Atirmociclib placebo (Other): Atirmociclib placebo tablet given twice a day

Primary outcomes

• Invasive Breast Cancer Free Survival (iBCFS) [Baseline until recurrence up to 64 months]: iBCFS is defined as the time from the date of randomization to the date of first documented occurrence of invasive ipsilateral breast tumor recurrence, local-regional invasive breast cancer recurrence, invasive contralateral breast cancer, distant recurrence, or death from any cause, as determined by investigator assessment per STEEP v2.0 criteria
• Invasive Disease Free Survival (iDFS) [Baseline until recurrence up to 64 months]: iDFS defined as the time from the date of randomization to the date of first documented occurrence of invasive ipsilateral breast tumor recurrence, local-regional invasive breast cancer recurrence, invasive contralateral breast cancer, distant recurrence, second primary invasive non-breast cancer, or death from any cause, as determined by investigator assessment per STEEP v2.0 criteria

Secondary outcomes

• Disease Recurrence Free Survival (DRFS) [Baseline until recurrence up to 64 months]: DRFS as per investigator assessment, defined as the time from the date of randomization to the date of distant recurrence as determined by investigator assessment or death from any cause, whichever occurs first
• Overall survival (OS) [Baseline until recurrence up to 64 months]: OS is defined as the time from the date of randomization to the date of death due to any cause
• Number and percentage of Participants with Treatment-Emergent Adverse Events (AEs) [Baseline until recurrence up to 64 months]: Type, incidence, severity of AE graded by NCI CTCAE v 5.0, seriousness and relationship to study intervention
• Percentage of participants With Clinical Laboratory Abnormalities [Baseline until recurrence up to 64 months]
• Percentage of Participants With ECG abnormalities [Baseline until recurrence up to 64 months]
• Patient Reported Outcomes (PRO) [Baseline until recurrence up to 64 months]: Change from baseline in participant reported total score, well-being subscales and symptoms scores and TOI per FACT-ES
• Pre-dose Plasma Concentration (Ctrough) of atirmociclib [Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 3 Day 1. Cycle is defined as 28 days]

Sex: All, ages: 18 Years to any

KEY INCLUSION CRITERIA

1. Histologically confirmed unilateral primary adenocarcinoma of the breast

   * ER-positive by local assessment
   * documented HER2-negative
2. Node positive or node negative as defined by:

   * Pathological node positive (microscopic and/or macroscopic tumor involvement >/=pN1)
   * pN0 and pT >1cm with at least one of the following:

     1. pT4N0 or
     2. histologically Grade 3 disease or
     3. high-risk classification based on genomic assay
3. Randomization within 16 months of definitive breast surgery
4. If indicated, completed adjuvant and/or neoadjuvant chemotherapy, adjuvant radiation therapy >/= 21 days prior to randomization

KEY EXCLUSION CRITERIA

1. Distant metastases of breast cancer beyond regional lymph nodes
2. Multicentric or multifocal breast cancer if any tumor foci meet pathologic criteria for ER(-) or HER2(+)
3. Clinically significant cardiovascular disease or cardiac repolarization abnormality for 6 months prior to randomization; resting heart rate <50bpm
4. Has received the following prior systemic anti-cancer therapy for breast cancer

   * prior atirmociclib, giredestrant, other investigational anti-cancer agent
   * prior treatment with olaparib

   NOTES:
   * short course of prior neo/adjuvant CDK4/6 inhibitor treatment (</=8 weeks) is permitted; 10-day washout period required
   * short course of prior neoadjuvant and/or adjuvant ET (</=18 weeks) is permitted; 35-day washout period for tamoxifen is required
5. Prior treatment with investigational product within 30 days or 5 half-lives

• Pfizer CT.gov Call Center, Study director, Pfizer