Clinical trial NCT04553133: PF-07104091 as a Single Agent and in Combination Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Ovarian Cancer
Breast Cancer
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-09-17
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
timeFrame: 28 days
measure: To evaluate incidence of treatment emergent adverse events and laboratory abnormalities
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline
timeFrame: From baseline until end of study treatment or study completion (approximately 2 years)
measure: To evaluate the preliminary antitumor activity of PF-07104091 as a single agent and in combination with palbociclib and in combination with letrozole or fulvestrant or fulvestrant alone by objective response rate (ORR) in dose expansion
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07104091
timeFrame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
measure: Area under the curve of PF-07104091 with or without food
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: Maximum plasma concentration of PF-07104091 with or without food
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
measure: To document any preliminary evidence of antitumor activity of PF-07104091 as a single agent and in combination with palbociclib and in combination with letrozole or fulvestrant or fulvestrant alone by objective response rate (ORR) in dose escalation
timeFrame: From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)
measure: To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints
timeFrame: From baseline through time to event on study or study completion (approximately 2 years)
Other outcomes:
Locations:
city: Clive
country: United States
facility: Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
state: Iowa
city: Des Moines
country: United States
facility: Des Moines Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute Downtown
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute Pharmacy, Downtown Pharmacy
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, Downtown
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews
state: Kentucky
city: Louisville
country: United States
facility: Norton Women's and Children's Hospital (St. Matthews)
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, Audubon
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital (Audubon)
state: Kentucky
city: Louisville
country: United States
facility: Norton Brownsboro Hospital
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, Brownsboro Campus
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: Long Island City
country: United States
facility: Memorial Sloan Kettering Cancer Center (IDS Pharmacy)
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center - NYU ACC
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center (Tisch Hospital)
state: New York
city: New York
country: United States
facility: MSK Rockefeller Outpatient Pavilion
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: White Plains
country: United States
facility: White Plains Hospital
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Charlottesville
country: United States
facility: UVA Breast Care Center
state: Virginia
city: Caba
country: Argentina
facility: Centro Oncologico Korben
state: Buenos Aires
city: Caba
country: Argentina
facility: Fundación Cenit Para La Investigación En Neurociencias
state: Ciudad Autónoma DE Buenos Aires
city: San Juan
country: Argentina
facility: Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology - Haskovo
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv EOOD
city: Shumen
country: Bulgaria
facility: Complex Oncology Center - Shumen
city: Changchun
country: China
facility: Jilin Province Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Koto
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: