pf-07104091 as a single agent and in combination therapy

Conditions: Small Cell Lung Cancer; Ovarian Cancer; Breast Cancer

Summary: 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.

Eligibility criteria:
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

Keywords: hormone receptor-positive human epidermal growth factor receptor 2 negative breast cancer cyclin-dependent kinase 2 inhibitor pf-07104091 palbociclib letrozole cyclin-dependent kinase ibrance