PF-07104091 as a Single Agent and in Combination Therapy

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Small Cell Lung Cancer; Ovarian Cancer
• Intervention / Treatment: Drug: PF-07104091 monotherapy dose escalation; 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-0704091 + Fulvestrant (post CDK4/6); Drug: PF-07104091 + Fulvestrant (post CDK4/6)

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 Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Not yet recruiting
      • Tianjin Medical University Cancer Institute & Hospital
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital of JFCR
• Mexico
  • Oaxaca, Mexico, 68000
    • Not yet recruiting
    • Oaxaca Site Management Organization
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 04700
      • Not yet recruiting
      • COI Centro Oncologico Internacional S.A.P.I. de C.V.
  • Nuevo LEÓN
    • Monterrey, Nuevo LEÓN, Mexico, 64460
      • Not yet recruiting
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
• United States
  • Iowa
    • Clive, Iowa, United States, 50325
      • Recruiting
      • Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
    • Des Moines, Iowa, United States, 50309
      • Recruiting
      • Des Moines Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • Recruiting
      • Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
    • Des Moines, Iowa, United States, 50314
      • Recruiting
      • Medical Oncology & Hematology Associates DBA Mission Cancer and Blood
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute, Downtown
    • Louisville, Kentucky, United States, 40241
      • Recruiting
      • Norton Brownsboro Hospital
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Hospital
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute, St. Matthews
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute Downtown
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute Pharmacy, Downtown Pharmacy
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Women's and Children's Hospital (St. Matthews)
    • Louisville, Kentucky, United States, 40217
      • Recruiting
      • Norton Cancer Institute, Audubon
    • Louisville, Kentucky, United States, 40217
      • Recruiting
      • Norton Hospital (Audubon)
    • Louisville, Kentucky, United States, 40241
      • Recruiting
      • Norton Cancer Institute, Brownsboro Campus
    • Louisville, Kentucky, United States, 40291
      • Recruiting
      • Norton Diagnostic Center - Fern Creek
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham & Women's Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth
  • New York
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester
    • Mineola, New York, United States, 11501
      • Recruiting
      • NYU Langone Hospital - Long Island
    • Mineola, New York, United States, 11501
      • Recruiting
      • Perlmutter Cancer Center at NYU Langone Hospital - Long Island
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center (Tisch Hospital)
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center - NYU ACC
    • New York, New York, United States, 10022
      • Recruiting
      • MSK Rockefeller Outpatient Pavilion
    • White Plains, New York, United States, 10601
      • Not yet recruiting
      • White Plains Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Not yet recruiting
      • University of Virginia Health System
    • Charlottesville, Virginia, United States, 22903
      • Not yet recruiting
      • University of Virginia Cancer Center
    • Charlottesville, Virginia, United States, 22911
      • Not yet recruiting
      • UVA Breast Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07104091; CDK2 monotherapy dose escalation	Drug: PF-07104091 monotherapy dose escalation; PF-07104091 will be administered orally
Experimental: PF-07104091 + palbociclib + fulvestrant; CDK2 + palbociclib + fulvestrant	Drug: PF-07104091 + palbociclib + fulvestrant; PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
Experimental: PF-07104091 + palbociclib + letrozole; CDK2 + palbociclib + letrozole	Drug: PF-07104091 + palbociclib + letrozole; PF-07104091 will be administered orally in combination with palbociclib and letrozole
Experimental: PF-07104091 monotherapy dose expansion (SCLC)	Drug: PF-07104091 monotherapy dose expansion (SCLC); PF-07104091 will be administered orally
Experimental: PF-07104091 monotherapy dose expansion (ovarian)	Drug: PF-07104091 monotherapy dose expansion (ovarian); PF-07104091 will be administered orally
Experimental: PF-07104091 + fulvestrant (post CDK4/6) dose expansion	Drug: PF-0704091 + Fulvestrant (post CDK4/6); PF-07104091 + fulvestrant (post 4/6) dose expansion
Experimental: PF-07104091 + fulvestrant (post CDK 4/6) dose escalation; CDK2+ fulvestrant (post CDK 4/6) dose escalation	Drug: PF-07104091 + Fulvestrant (post CDK4/6); PF-07104091 will be administered orally in combination with fulvestrant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Anticipated): January 7, 2025
• Study Completion (Anticipated): January 7, 2026

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: letrozole; Ibrance; palbociclib; Hormone receptor-positive human epidermal growth factor receptor 2 negative breast cancer; Cyclin-Dependent Kinase 2 Inhibitor; PF-07104091; cyclin-dependent kinase
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Letrozole; Fulvestrant; Palbociclib
• Other Study ID Numbers: C4161001; 2022-001679-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No