Resumen

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. The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide. In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively). In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A. Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC. Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively. Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide. Part 2E is an expansion cohort to evaluate PF-07220060 Monotherapy versus PF-07220060 plus fulvestrant combination therapy. The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants. The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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, 2C and 2E:
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, 2C and 2E: 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 and 2E: 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
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

Criterios de exclusión

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

Ubicaciones

Hospital Británico de Buenos Aires

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Fundación Cenit Para La Investigación En Neurociencias

CABA, Ciudad Autã³noma de Buenos Aires, Argentina

Fundación Respirar

Buenos Aires, Argentina

Clínica Universitaria Reina Fabiola

Córdoba, Argentina

Fundación CORI para la Investigación y Prevención del Cáncer

La Rioja, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

PF-07220060

Letrozole

Fulvestrant

Midazolam

Enzalutamide