PF-07104091 as a Single Agent and in Combination Therapy

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04553133
• Other study ID #: C4161001
• Secondary ID: 2022-001679-15
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 16, 2020
• Est. completion date: March 6, 2025

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 154
• Est. completion date: March 6, 2025
• Est. primary completion date: March 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Ovarian Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• PF-07104091 monotherapy dose escalation
PF-07104091 will be administered orally
• PF-07104091 + palbociclib + fulvestrant
PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
• PF-07104091 + palbociclib + letrozole
PF-07104091 will be administered orally in combination with palbociclib and letrozole
• PF-07104091 monotherapy dose expansion (ovarian)
PF-07104091 will be administered orally
• PF-07104091 monotherapy dose expansion (SCLC)
PF-07104091 will be administered orally
• PF-07104091 + Fulvestrant (post CDK4/6)
PF-07104091 will be administered orally in combination with fulvestrant
• PF-0704091 + Fulvestrant (post CDK4/6)
PF-07104091 + fulvestrant (post 4/6) dose expansion

Locations

Country	Name	City	State
Argentina	Centro Oncologico Korben	Caba	Buenos Aires
Argentina	Fundación Cenit Para La Investigación En Neurociencias	Caba	Ciudad Autónoma DE Buenos Aires
Argentina	Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan	San Juan
Bulgaria	Specialized Hospital for Active Treatment of Oncology - Haskovo	Haskovo
Bulgaria	Complex Oncology Center - Plovdiv EOOD	Plovdiv
Bulgaria	Complex Oncology Center - Shumen	Shumen
China	Jilin Province Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou
China	Henan Cancer Hospital	Zhengzhou	Henan
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	The Cancer Institute Hospital of JFCR	Koto	Tokyo
Mexico	COI Centro Oncologico Internacional S.A.P.I. de C.V.	Mexico City	Distrito Federal
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEÓN
Mexico	Oaxaca Site Management Organization	Oaxaca
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	University of Virginia Health System	Charlottesville	Virginia
United States	UVA Breast Care Center	Charlottesville	Virginia
United States	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Clive	Iowa
United States	Des Moines Oncology Research Association	Des Moines	Iowa
United States	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Des Moines	Iowa
United States	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Des Moines	Iowa
United States	START Midwest	Grand Rapids	Michigan
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center (IDS Pharmacy)	Long Island City	New York
United States	Norton Brownsboro Hospital	Louisville	Kentucky
United States	Norton Cancer Institute Downtown	Louisville	Kentucky
United States	Norton Cancer Institute Pharmacy, Downtown Pharmacy	Louisville	Kentucky
United States	Norton Cancer Institute, Audubon	Louisville	Kentucky
United States	Norton Cancer Institute, Brownsboro Campus	Louisville	Kentucky
United States	Norton Cancer Institute, Downtown	Louisville	Kentucky
United States	Norton Cancer Institute, St. Matthews	Louisville	Kentucky
United States	Norton Diagnostic Center - Fern Creek	Louisville	Kentucky
United States	Norton Hospital	Louisville	Kentucky
United States	Norton Hospital (Audubon)	Louisville	Kentucky
United States	Norton Women's and Children's Hospital (St. Matthews)	Louisville	Kentucky
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Perlmutter Cancer Center at NYU Langone Hospital - Long Island	Mineola	New York
United States	Laura & Isaac Perlmutter Cancer Center - NYU ACC	New York	New York
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	MSK Rockefeller Outpatient Pavilion	New York	New York
United States	NYU Langone Medical Center (Tisch Hospital)	New York	New York
United States	Dana-Farber Cancer Institute - Chestnut Hill	Newton	Massachusetts
United States	White Plains Hospital	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  China,  Japan,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle	Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level	28 days
Primary	To evaluate incidence of treatment emergent adverse events and laboratory abnormalities	Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities will be summarized by dose level	From baseline until end of study treatment or study completion (approximately 2 years)
Primary	Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline	Identify pulse rate readings that are outside the normal range. The number and percentage of participants who experienced significant pulse rate change from baseline will be summarized by dose level	From baseline until end of study treatment or study completion (approximately 2 years)
Primary	Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline	Identify systolic and diastolic readings that are outside the normal range. The number and percentage of participants who experienced significant blood pressure change from baseline will be summarized by dose level	From baseline until end of study treatment or study completion (approximately 2 years)
Primary	To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline	Determine the effect of the drug on QT prolongation. The number and percentage of participants who experienced QT interval prolongation will be summarized by dose level	From baseline until end of study treatment or study completion (approximately 2 years)
Primary	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	Percentage of participants with a best overall response of complete response (CR) or partial response (PR) using RECIST 1.1	From baseline through disease progression or study completion (approximately 2 years)
Secondary	Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose	Peak concentration of PF-07104091 during selected cycles	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose	Time to peak concentration of PF-07104091 during selected cycles	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	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	AUC of PF-07104091 will be calculated at selected cycles	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Area under the curve of PF-07104091 with or without food	AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food	From baseline through time to event on study or study completion (approximately 2 years)
Secondary	Maximum plasma concentration of PF-07104091 with or without food	Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food	From baseline through time to event on study or study completion (approximately 2 years)
Secondary	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	Percentage of participants with a best overall response of CR or PR using RECIST 1.1	From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)
Secondary	To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints	Time from first assessment of event endpoint to last assessment of using RECIST 1.1	From baseline through time to event on study or study completion (approximately 2 years)

External Links

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