PF-07104091 as a Single Agent and in Combination Therapy

Phase 1

Active, not recruiting

• Conditions: Breast Cancer; Small Cell Lung Cancer; Ovarian Cancer
• Interventions: Drug: PF-07104091 monotherapy dose escalation; Drug: PF-0704091 + Fulvestrant (post CDK4/6); Drug: PF-07104091 + palbociclib + fulvestrant; Drug: PF-07104091 + palbociclib + letrozole; Drug: PF-07104091 monotherapy dose expansion (SCLC); Drug: PF-07104091 monotherapy dose expansion (ovarian); Drug: PF-07104091 + Fulvestrant (post CDK4/6)

• Registration Number: NCT04553133
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2020-08-21
• Study First Submitted QC: 2020-09-11
• Study Start: 2020-09-16
• Study First Posted: 2020-09-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16
• Primary Completion: 2025-03-06
• Study Completion: 2025-03-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 154

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PF-07104091	PF-07104091 monotherapy dose escalation	CDK2 monotherapy dose escalation
PF-07104091 + fulvestrant (post CDK4/6) dose expansion	PF-0704091 + Fulvestrant (post CDK4/6)	PF-07104091 + fulvestrant (post CDK4/6) dose expansion
PF-07104091 + palbociclib + fulvestrant	PF-07104091 + palbociclib + fulvestrant	CDK2 + palbociclib + fulvestrant
PF-07104091 + palbociclib + letrozole	PF-07104091 + palbociclib + letrozole	CDK2 + palbociclib + letrozole
PF-07104091 monotherapy dose expansion (SCLC)	PF-07104091 monotherapy dose expansion (SCLC)	PF-07104091 monotherapy dose expansion (SCLC)
PF-07104091 monotherapy dose expansion (ovarian)	PF-07104091 monotherapy dose expansion (ovarian)	PF-07104091 monotherapy dose expansion (ovarian)
PF-07104091 + fulvestrant (post CDK 4/6) dose escalation	PF-07104091 + Fulvestrant (post CDK4/6)	CDK2+ fulvestrant (post CDK 4/6) dose escalation

Primary Outcome Measures

Name	Time	Method
Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline	From baseline until end of study treatment or study completion (approximately 2 years)	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
Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline	From baseline until end of study treatment or study completion (approximately 2 years)	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
To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline	From baseline until end of study treatment or study completion (approximately 2 years)	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
Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle	28 days	Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level
To evaluate incidence of treatment emergent adverse events and laboratory abnormalities	From baseline until end of study treatment or study completion (approximately 2 years)	Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities will be summarized by dose level
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	From baseline through disease progression or study completion (approximately 2 years)	Percentage of participants with a best overall response of complete response (CR) or partial response (PR) using RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Area under the curve of PF-07104091 with or without food	From baseline through time to event on study or study completion (approximately 2 years)	AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
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	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)	AUC of PF-07104091 will be calculated at selected cycles
Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)	Peak concentration of PF-07104091 during selected cycles
Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose	Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)	Time to peak concentration of PF-07104091 during selected cycles
Maximum plasma concentration of PF-07104091 with or without food	From baseline through time to event on study or study completion (approximately 2 years)	Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
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	From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)	Percentage of participants with a best overall response of CR or PR using RECIST 1.1
To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints	From baseline through time to event on study or study completion (approximately 2 years)	Time from first assessment of event endpoint to last assessment of using RECIST 1.1

Trial Locations

Locations (49)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Tianjin Medical University Cancer Institute & Hospital; 🇨🇳 Tianjin, Tianjin, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Des Moines Oncology Research Association; 🇺🇸 Des Moines, Iowa, United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham & Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States

NYU Langone Medical Center (Tisch Hospital); 🇺🇸 New York, New York, United States

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Memorial Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Specialized Hospital for Active Treatment of Oncology - Haskovo; 🇧🇬 Haskovo, Bulgaria

Jilin Province Cancer Hospital; 🇨🇳 Changchun, Jilin, China

White Plains Hospital; 🇺🇸 White Plains, New York, United States

UVA Breast Care Center; 🇺🇸 Charlottesville, Virginia, United States

Oaxaca Site Management Organization; 🇲🇽 Oaxaca, Mexico

MSK Rockefeller Outpatient Pavilion; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Centro Oncologico Korben; 🇦🇷 Caba, Buenos Aires, Argentina

Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan; 🇦🇷 San Juan, Argentina

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

Medical Oncology & Hematology Associates DBA Mission Cancer and Blood; 🇺🇸 Des Moines, Iowa, United States

Dana-Farber Cancer Institute - Chestnut Hill; 🇺🇸 Newton, Massachusetts, United States

Laura & Isaac Perlmutter Cancer Center - NYU ACC; 🇺🇸 New York, New York, United States

NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

Memorial Sloan Kettering Cancer Center (IDS Pharmacy); 🇺🇸 Long Island City, New York, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Complex Oncology Center - Shumen; 🇧🇬 Shumen, Bulgaria

The Cancer Institute Hospital of JFCR; 🇯🇵 Koto, Tokyo, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"; 🇲🇽 Monterrey, Nuevo LEÓN, Mexico

Norton Cancer Institute Downtown; 🇺🇸 Louisville, Kentucky, United States

Norton Cancer Institute Pharmacy, Downtown Pharmacy; 🇺🇸 Louisville, Kentucky, United States

Norton Cancer Institute, Downtown; 🇺🇸 Louisville, Kentucky, United States

Norton Hospital; 🇺🇸 Louisville, Kentucky, United States

Norton Cancer Institute, St. Matthews; 🇺🇸 Louisville, Kentucky, United States

Norton Women's and Children's Hospital (St. Matthews); 🇺🇸 Louisville, Kentucky, United States

Norton Cancer Institute, Audubon; 🇺🇸 Louisville, Kentucky, United States

Norton Hospital (Audubon); 🇺🇸 Louisville, Kentucky, United States

Norton Brownsboro Hospital; 🇺🇸 Louisville, Kentucky, United States

Norton Cancer Institute, Brownsboro Campus; 🇺🇸 Louisville, Kentucky, United States

Norton Diagnostic Center - Fern Creek; 🇺🇸 Louisville, Kentucky, United States

COI Centro Oncologico Internacional S.A.P.I. de C.V.; 🇲🇽 Mexico City, Distrito Federal, Mexico

Complex Oncology Center - Plovdiv EOOD; 🇧🇬 Plovdiv, Bulgaria

Fundación Cenit Para La Investigación En Neurociencias; 🇦🇷 Caba, Ciudad Autónoma DE Buenos Aires, Argentina