A Phase 1/2A Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of PF-07220060 as a Single Agent and as Part of Combination Therapy in Participants with Advanced Solid Tumors

This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety,
tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a
single agent and then in combination with endocrine therapy.

Inclusion Criteria

- Part 1: Breast Cancer (BC)

- Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor
Receptor 2 Negative (HER2-) BC

- Part 1A/Part 1D/Part1E also include: Refractory HR-positive/HER2-positive BC

- Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC,
liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according
to local standard tests

- Part 1F: prostate cancer

- Part 2A, 2B and 2C:

- HR-positive/HER2-negative BC

- Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C
only)

- Part 1D: metastatic castration resistant prostate cancer

- Lesion:

- Part 1: evaluable lesion (including skin or bone lesion only)

- Part 2A, 2B and 2C: measurable lesion per RECIST v1.1

- Part 2D: Participants with evaluable disease as per PCWG3; participants with bone
metastases only are allowed. Participants with biochemical recurrence only are
excluded.

- Prior systemic Treatment

- Part 1: HR-positive/HER2-negative BC

- At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or
metastatic disease, or if CDK4/6 inhibitors are not considered appropriate
in the opinion of the investigator

- At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor
approval or reimbursement, for advanced or metastatic disease

- HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of
approved HER2 targeting therapy

- Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at
least 2 lines of SOC for advanced or recurrent disease or for which no
standard therapy is available

- Part 2A: participants must have received at least 1 line of standard of care
(including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is
allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed

- Part 2B: participants who have not received any prior systemic anti-cancer
therapies for advanced/metastatic BC

- Part 2C:

- Progressed during treatment or within 12 months of completion of adjuvant
therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre
or perimenopausal, or

- Progressed while on or within 1 month after the endo the prior aromatase
inhibitor therapy for advanced/metastatic BC if postmenopausal or prior
endocrine treatment for advanced/metastatic BC if pre or perimenopausal

- One previous line of chemotherapy for advanced/metastatic disease is allowed
in addition to endocrine therapy

- Part 2D:

- Received prior abiraterone; enzalutamide and CDK4i naive

- 0-1 line of chemotherapy is allowed General Inclusion Criteria

- All participants must be refractory to or intolerant of existing therapies known to
provide clinical benefit for their condition.

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

- Adequate renal, liver, and bone marrow function

Exclusion Criteria:

- Part 1D: participants who have had a gastrectomy or have dietary or other restrictions
that preclude a 10 hour overnight fast or consumption of the high fat, high calorie
meal

- Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase
inhibitor with disease recurrence while on or within 12 months of completing
treatment. Prior treatment with any CDK4/6 inhibitor

- Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent
whose mechanism of action is to inhibit the PI3K-mTOR pathway

- Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases
carcinomatous meningitis, or leptomeningeal disease

- Other active malignancy within 3 years prior to randomization, except for adequately
treated basal cell or squamous cell skin cancer, or carcinoma in situ

- Major surgery or radiation within 4 weeks prior to study intervention

- Last anti-cancer treatment within 2 weeks prior to study intervention

- Participation in other studies involving investigational drug(s) within 4 weeks prior
to study entry

- Pregnant or breastfeeding female participant

- Active inflammatory gastrointestinal (GI) disease, known diverticular disease or
previous gastric resection or lap band surgery including impairment of
gastrointestinal function or GI disease