Study of PF-07248144 in Advanced or Metastatic Solid Tumors

JRCT ID: jRCT2031200246

Registered date:15/12/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Locally Advanced or Metastatic ER+ HER2- Breast Cancer, CRPC, NSCLC
• Date of first enrollment: 16/11/2020
• Target sample size: 186
• Countries of recruitment: United States,Japan,Australia,Japan,South Korea,Japan,China,Japan
• Study type: Interventional

Intervention(s)

Part 1A: PF-07248144 (KAT6 Inhibitor)
Part 1B: PF-07248144 (KAT6 Inhibitor), Fulvestrant (Endocrine Therapy: Faslodex)
Part 1C: PF-07248144 (KAT6 Inhibitor), Letrozole (Endocrine Therapy: Femara), Palbociclib (CDK4/6 Inhibitor: Ibrance)
Part 1D: PF-07248144 (KAT6 Inhibitor), PF-07220060 (CDK4 Inhibitor), Fulvestrant (Endocrine Therapy: Faslodex)
Part 2A: PF-07248144 (KAT6 Inhibitor)
Part 2B: PF-07248144 (KAT6 Inhibitor), Fulvestrant (Endocrine Therapy: Faslodex)
Part 2D: PF-07248144 (KAT6 Inhibitor), PF-07220060 (CDK4 Inhibitor), Fulvestrant (Endocrine Therapy: Faslodex)

Outcome(s)

Primary Outcome

1. Number of participants with dose-limiting toxicities in the Dose Escalation Arms. [ Time Frame: Up to 29 days ]
Dose-limiting toxicities (DLTs)
2. Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
3. Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. [ Time Frame: Up to 24 months ]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
4. Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
5. Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Secondary Outcome

1. Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
2. Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
3. Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
4. Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
5. Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
6. Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
7. Multiple Dose: Steady state AUC during a dosage interval (tau) (AUCtau,ss) in the Dose Escalation and Dose Finding Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
8. Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
9. Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms. [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessments for PF-07248144
10. Best Overall Response (BOR) in participants in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
11. Duration of Response (DOR) in participants enrolled in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
12. Peak concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessment for PF-07248144
13. Trough concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms [ Time Frame: Up to 24 months ]
Pharmacokinetic (PK) assessment for PF-07248144
14. Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
The effect of food on the PK of PF-07248144.
15. Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
The effect of food on the PK of PF-07248144.
16. AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm [ Time Frame: Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) ]
The effect of food on the PK of PF 07248144.
17. Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
18. Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms [ Time Frame: Up to 24 months ]
19.Overall survival (OS) observed in participants enrolled in Dose Expansion Arms [ Time Frame: Up to 24 months ]

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Disease Characteristics - Breast, Prostate, and Lung Cancer
*Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer, locally advanced or metastatic CRPC, or locally advanced or metastatic NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available.
*Part 1B, Part 1C and Part 1D (Combination Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting.
*Part 2A (ER+HER2- breast cancer 3L+, monotherapy) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 lines of endocrine therapy.
*Part 2B (ER+HER2- breast cancer 2L, combination) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after 1 prior line of CDK4/6 inhibitor and at least 1 line of endocrine therapy.
*Part 2D (ER+HER2- breast cancer 2L, combination) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and at least 1 line of endocrine therapy.
*Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of ER-positive tumor (>=1% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards.
*Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4.
*Female participants with ER+HER2- advanced or metastatic breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause by treatment with the approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause.
*Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that 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).
*Adequate renal, liver, and bone marrow function.
*Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for adverse events (AEs) not constituting a safety risk by investigator judgment.I136

Exclude criteria

*Unmanageable ascites (limited medical treatment to control ascites is permitted, but all 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 carcinoma in situ.
*Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior 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 myocardial infarction or active myocardia ischemia).
*Therapeutic anticoagulation. However, low molecular weight heparin is allowed. Vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor.
*Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of PF-07248144.
*Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous gastric resection, lap band surgery or other GI conditions and surgeries that may significantly alter the absorption of PF-07248144 tablets. Gastroesophageal reflux disease under treatment is allowed.
*Pregnant or breastfeeding female participants.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT04606446