Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors

JRCT ID: jRCT2031230121

Registered date:07/06/2023

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: advanced or metastatic BC, prostate cancer or other solid tumor
• Date of first enrollment: 08/06/2023
• Target sample size: 337
• Countries of recruitment: United States,Japan,Argentina,Japan,China,Japan,Czechia,Japan,Mexico,Japan,Slovakia,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

* Part 1A/1D/1E: PF-07220060 (CDK4 inhibitor)
* Part 1B/2B: PF-07220060 + Letrozole
* Part 1C/2A/2C: PF-07220060 + Fulvestrant
* Part 1F/2D: PF-07220060 + Enzalutamide

Outcome(s)

Primary Outcome

* Number of participants with DLT in the dose escalation portion [Time Frame: Baseline up to day 28 of Cycle 1] (Part 1A/1B/1C/1F)
* Incidence of clinically significant AEs, laboratory abnormalities and vital sign abnormalities [Time Frame: Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days] (Part 1)
* Incidence of clinically significant abnormal ECG parameters [Time Frame: Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days)] (Part 1)
* Food effect on PK parameters including Cmax, Tmax, AUC [Time Frame: Day -7 through the end of Cycle 1] (Part 1D)
* PF-07220060's effect on PK parameters of midazolam (CYP3A4 probe substrate) including Cmax, Tmax, AUC [Time Frame: Day -1 through the end of Cycle 1] (Part 1E)

Secondary Outcome

Part 1 Dose escalatoin portion
* PK parameter of single dose: Cmax; Tmax; AUClast; AUCinf; CL/F; Vz/F; and t1/2 (Parts 1A/1B/1C/1F)
* PK parameter of multiple dose: Css,max; Tss,max; AUCss,t; Css,min; CLss/F; Vss/F; t1/2; and Rac (AUCss,t /AUCsd,t) (Parts 1A/1B/1C/1E/1F)
* PK parameter of enzalutamide (Part 1F)
[Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months]
* Objective response rate (ORR) per RECIST v1.1 (Part 1A-E) or PCGW3 (Part 1F)

Part 2 Dose expansion portion
* ORR, Duration of Response (DOR), Progression Free Survival (PFS), Time to Progression (TTP), Clinical Benefit Rate (CBR) per RECIST v1.1 (Parts 2A/2B/2C)
* ORR, DOR by PCWG3, PSA50 rate, rPFS, Time to first skeletal related events (Part 2D)
* Symptoms and Health-Related Quality of Life (Part 2D)
[Time Frame: baseline up to approximately 24 months]
* Peak and Trough Concentration of PF-07220060 (Parts 2A/2B/2C/2D) and enzalutamide (Part 2D)
[Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Disease
* Part 1A/1D/1E: HR+HER2-BC, HR+HER2+BC, NSCLC, prostate cancer, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests
* Part 1B/1C: HR+HER2-BC
* Part 1F: Prostate cancer
* Part 2A/2B/2C: HR+HER2-BC
* Part 2D: CRPC
Lesion
* Part 1: evaluable lesion (including skin or bone lesion only)
* Part 2A/2B/2C: measurable lesion per RECIST v1.1
* Part 2D: evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded
Prior systemic treatment
* Part 1: Refractory to or intolerant of existing standard therapies including CDK4/6i, HER2 targeting therapy or approved systemic therapy, or no standard therapy is available
* Part 2A: Must have at least 1 line of SOC, including prior CDK4/6i, for advanced/metastatic BC (Prior chemotherapies for advanced disease setting are allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed)
* Part 2B: No 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 end of the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or 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 treatment with abiraterone in any setting; No prior enzalutamide and CDK4/6i (up to 1 prior line of chemotherapy in any setting is allowed)
General inclusion criteria
* ECOG PS 0 or 1
* Adequate renal, liver, and bone marrow function

Exclude 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

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT04557449