Clinical Research Directory

Inclusion Criteria * 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 Exclusion Criteria: * 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