Study to Assess the Safety and Tolerability of PF-07220060 in Combination With PF-07104091 in Participants With Breast Cancers or Solid Tumors and to Assess the Safety and Tolerability of PF-07220060 and PF-07104091 in Combination With Endocrine The

• Status: Not yet recruiting
• Trial end date: 2027-11-03
• Target enrollment: 0
• Participant gender: All

Summary

To assess the safety and tolerability of increasing doses of PF-07220060 in combination with PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended dose for expansion (RDE) for PF-07220060 in combination with PF-07104091 in participants with breast cancers or solid tumors and to assess the safety and tolerability of the RDE of PF-07220060 and PF-07104091 in combination with Endocrine Therapy in participants with breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pfizer
• Treatments: Fulvestrant; Letrozole

Criteria

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 2A and 2B: At least 1 prior endocrine therapy for advanced or metastatic disease.

• 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: Prior treatment with any CDK 4/6 inhibitor, or fulvestrant, or everolimus.

• Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor 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.

• 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