Study of PF-07248144 in Advanced or Metastatic Solid Tumors

Inclusion Criteria:

• Disease Characteristics - Breast, Prostate, and Lung Cancer

• Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis oflocally advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC that isintolerant or resistant to standard therapy or for which no standard therapy isavailable.

• Part 1B, Part 1C and Part 1D (Combination Dose Escalation) Histological orcytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer.Participants must have progressed after at least 1 prior line of treatment with anendocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting.

• Part 2A (ER+HER2- breast cancer 2L+, monotherapy) Histological or cytologicaldiagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participantsmust have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 line ofendocrine therapy.

• Part 2B (ER+HER2- breast cancer 2-4L, combination with fulvestrant) Histological orcytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participantsmust have progressive disease after at least 1 prior line of a CDK4/6 inhibitor andat least 1 prior line of endocrine therapy.. Participants must not have receivedmore than 3 prior lines of systemic therapies including up to 1 line of cytotoxicchemotherapy for visceral disease in advanced or metastatic setting; Participantsmay have but are not required to have prior treatment with fulvestrant.

• Part 2D (ER+HER2- breast cancer 2-4L, combination with PF-07220060 (CDK4i) andfulvestrant):

Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.

• Participants must have not received more than 3 lines of systemic therapiesincluding up to 1 line of cytotoxic chemotherapy for visceral disease in advanced ormetastatic setting; Participants may have but are not required to have priortreatment with fulvestrant.

• Participants with ER+HER2- advanced or metastatic breast cancer must havedocumentation of ER-positive tumor (≥1% positive stained cells) based on most recenttumor biopsy utilizing an assay consistent with local standards.

• Participants with ER+HER2- advanced or metastatic breast cancer must havedocumentation of HER2-negative tumor: HER2-negative tumor is determined asimmunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio <2 or for single probeassessment a HER2 copy number <4.

• Female participants with ER+HER2- advanced or metastatic breast cancer considered tobe of childbearing potential (or have tubal ligations only) must be willing toundergo medically induced menopause by treatment with the approved LHRH agonist suchas goserelin, leuprolide or equivalent agents to induce chemical menopause.

• Female participants with ER+HER2- advanced or metastatic breast cancer ofnonchildbearing potential must meet at least 1 criteria of achieving postmenopausalstatus.

• Participants must have at least 1 measurable lesion as defined by RECIST version 1.1that has not been previously irradiated.

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

• Female or male patients aged ≥ 18 years (Japan ≥ 20 years) (South Korea ≥ 19 years).

• Adequate renal, liver, and bone marrow function.

• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1except for adverse events (AEs) not constituting a safety risk by investigatorjudgment.

Exclusion Criteria:

• Unmanageable ascites (limited medical treatment to control ascites is permitted, butall participants with ascites require review by sponsor's medical monitor).

• Participants with any other active malignancy within 3 years prior to enrollment,except for adequately treated basal cell or squamous cell skin cancer, or carcinomain situ.

• Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeksprior to study entry.

• Prior irradiation to >25% of the bone marrow.

• ECG clinically relevant abnormalities (eg, QTc >470 msec, complete LBBB,second/third degree AV block, ST elevation or EKG changes suggesting myocardialinfarction or active myocardia ischemia).

• Therapeutic anticoagulation. However, low molecular weight heparin is allowed.Vitamin K antagonists or factor Xa inhibitors may be allowed following discussionwith the Sponsor.

• Known or suspected hypersensitivity or severe allergy to activeingredient/excipients of PF-07248144.

• Active inflammatory GI disease, refractory and unresolved chronic diarrhea orprevious gastric resection, lap band surgery or other GI conditions and surgeriesthat may significantly alter the absorption of PF-07248144 tablets. Gastroesophagealreflux disease under treatment is allowed.

• Pregnant or breastfeeding female participants.