A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors

Open to people ages 18 years and up

• Part 1: Breast Cancer (BC)
• HR+, HER2- BC
• Refractory HR-positive/HER2-positive BC
• Part 1: Solid Tumors other than BC
• Part 2:
• HR-positive/HER2-negative BC
• Lesion:
• Part 1: evaluable lesion (including skin or bone lesion only)
• Part 2: measurable lesion per RECIST v1.1
• Prior systemic Treatment
• Part 1: HR-positive/HER2-negative BC
• At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease.
• Prior chemotherapy in the metastatic setting is allowed.
• Part 1: HR-positive/HER2-positive BC
• At least 1 prior treatment of approved HER2 targeting therapy.
• Part 1: Solid Tumors other than BC
• Participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator.
• Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET.
• Parts 2B: At least 1 prior endocrine therapy for advanced or metastatic disease. Progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable.
• Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed.
• General Inclusion Criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• Adequate renal, liver, and bone marrow function
• Resolved acute effects of any prior therapy to baseline severity

• All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
• Part 2B and 1C: Prior treatment with any CDK 4/6 inhibitor, or SERDs (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway for advanced disease.
• Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
• Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
• Part 2C: Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
• Part 2C: Any prior systemic treatment for advanced disease.
• Prior irradiation to >25% of the bone marrow
• Current use of drugs which have a risk for QTc prolongation
• Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers
• Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
  • Participants with any other active malignancy within 3 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease
  • Major surgery within 4 weeks prior to study entry
  • Radiation therapy within 4 weeks prior to study entry.
  • Clinically important hypertension
  • Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)
• Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases
• Active inflammatory GI disease
• Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention
• Previous high-dose chemotherapy requiring stem cell rescue
• Participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• Other protocol specific exclusion criteria may apply