PF-07104091 as a Single Agent and in Combination Therapy

PHASE 1/2A DOSE ESCALATION, FINDING AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07104091 AS A SINGLE AGENT AND IN COMBINATION THERAPY

To assess the safety and tolerability of increasing doses of PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended Phase 2 dose (RP2D) for PF-07104091 as a single agent in participants with advanced or metastatic small cell lung, breast and ovarian cancers.

Study C4161001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-07104091 in adult patients with advanced or metastatic small cell lung cancer (SCLC), advanced platinum resistant epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, locally recurrent/advanced or metastatic triple negative breast cancer (TNBC), HR-positive HER2-negative advanced or mBC, advanced or metastatic non-small cell lung cancer (NSCLC). This two part study will assess the safety and tolerability of increasing dose levels of PF-07104091 in Part 1, and establish the recommended Phase 2 dose (RP2D) in Part 2.

Inclusion Criteria:

• Participants with HR-positive HER2-negative advanced or metastatic breast cancer (received at least two prior lines in the advanced or metastatic setting including one prior line of combined CDK4/6 inhibitor and endocrine therapy and no more than two prior lines of cytotoxic chemotherapy)
• Participants with locally recurrent/advanced or metastatic TNBC who have received up to 2 prior lines of chemotherapy in the advanced or metastatic setting
• Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven) who have received at least 1 systemic anti-cancer therapy containing a platinum analog
• Participants with cytological diagnosis of advanced/metastatic SCLC
• Participants with or cytological diagnosis of advanced/metastatic NSCLC
• Participants with HR-positive HER2-negative advanced or metastatic breast cancer (second line plus setting) (histologically or cytologically proven).
• Participants entering the study in the expansion cohort have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated
• Performance Status 0 or 1
• Adequate bone marrow, hematological, kidney and liver function
• Resolved acute effects of any prior therapy to baseline severity

Exclusion Criteria:

• Participants with known symptomatic brain metastases requiring steroids
• Participants with any other active malignancy within 3 years prior to enrollment
• Major surgery within 3 weeks prior to study entry
• Radiation therapy within 3 weeks prior to study entry.
• Systemic anti cancer therapy within 4 weeks prior to study
• Prior irradiation to >25% of the bone marrow
• Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, and known HIV or AIDS related illness
• Active COVID-19/SARS-CoV2 infection
• Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
• Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, arrhythmias, serious conduction system abnormalities, unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo embolic disease.
• Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed.
• Hypertension that cannot be controlled by medications
• Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.
• Known or suspected hypersensitivity to active ingredient/excipients in PF 07104091.
• Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
• Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short
• Participants with an indwelling catheter that has an external component such as those used for drainage of effusion(s) or central venous catheter that is externally
• Previous high dose chemotherapy requiring stem cell rescue
• Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin (if applicable).
• Current use or anticipated need for food or drugs that are known strong CYP3A4/5 or UGT1A9 inhibitors or inducers
• Current use or anticipated need for drugs that are known sensitive UGT1A1 substrates with narrow therapeutic
• Serum pregnancy test positive at screening
• Other medical or psychiatric condition