PF-07104091 as a Single Agent and in Combination Therapy

• ClinicalTrials.gov Identifier: NCT04553133
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2020
• Last Update Posted: May 16, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 21, 2020
• First Posted Date: September 17, 2020
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: September 16, 2020
• Estimated Primary Completion Date: March 6, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2023)

• Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle [ Time Frame: 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 [ Time Frame: 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
• Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
• 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 [ Time Frame: 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

Original Primary Outcome Measures (submitted: September 11, 2020)

• Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle [ Time Frame: 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 [ Time Frame: 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
• Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
• To evaluate the preliminary antitumor activity of PF-07104091 as a single agen and in combination with palbociclib and in combination with letrozole by objective response rate (ORR) in dose expansion [ Time Frame: 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

Current Secondary Outcome Measures (submitted: March 8, 2023)

• Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose [ Time Frame: 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 [ Time Frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
  Time to peak concentration of PF-07104091 during selected cycles
• 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 [ Time Frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
  AUC of PF-07104091 will be calculated at selected cycles
• Area under the curve of PF-07104091 with or without food [ Time Frame: 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
• Maximum plasma concentration of PF-07104091 with or without food [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: September 11, 2020)

• Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose [ Time Frame: 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 [ Time Frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
  Time to peak concentration of PF-07104091 during selected cycles
• 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 [ Time Frame: Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
  AUC of PF-07104091 will be calculated at selected cycles
• Area under the curve of PF-07104091 with or without food [ Time Frame: 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
• Maximum plasma concentration of PF-07104091 with or without food [ Time Frame: 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 agen and in combination with palbociclib and in combination with letrozole by objective response rate (ORR) in dose escalation [ Time Frame: 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 [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Small Cell Lung Cancer
• Ovarian Cancer
• Breast Cancer

Intervention

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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 14, 2024): 154
• Original Estimated Enrollment (submitted: September 11, 2020): 144
• Estimated Study Completion Date: March 6, 2025
• Estimated Primary Completion Date: March 6, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, China, Japan, Mexico, United States

Administrative Information

• NCT Number: NCT04553133
• Other Study ID Numbers: C4161001; 2022-001679-15 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2024