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PF-07104091 as a Single Agent and in Combination Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04553133
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : November 3, 2020
Sponsor:
Information provided by (Responsible Party):
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 small cell lung, non small cell lung ovarian and breast cancers.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Ovarian Cancer Triple Negative Breast Cancer Non-small Cell Lung Cancer Human Receptor-positive Human Epidermal Growth Factor Receptor 2 Drug: PF-07104091 monotherapy Drug: PF-07104091 + palbociclib Drug: PF-07104091 + palbociclib + letrozole Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : April 18, 2025
Estimated Study Completion Date : April 18, 2025


Arm Intervention/treatment
Experimental: PF-07104091
CDK2 monotherapy
Drug: PF-07104091 monotherapy
PF-07104091 will be administered orally

Experimental: PF-07104091 + palbociclib
CDK2 + palbociclib
Drug: PF-07104091 + palbociclib
PF-07104091 will be administered orally in combination with palbociclib

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




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 up to 3 prior lines of therapy
  • Participants with cytological diagnosis of advanced/metastatic SCLC
  • Participants with or cytological diagnosis of advanced/metastatic NSCLC
  • 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
  • COVID-19/SARS-CoV2
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04553133


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
United States, Tennessee
Tennessee Oncology PLLC Not yet recruiting
Franklin, Tennessee, United States, 37067
Tennessee Oncology, PLLC Not yet recruiting
Nashville, Tennessee, United States, 37203
The Sarah Cannon Research Institute Not yet recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04553133    
Other Study ID Numbers: C4161001
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: October 2020
Individual Participant Data (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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Small cell lung cancer
Ovarian cancer
Triple negative breast cancer
Human receptor-positive human epidermal growth factor receptor 2
Non-small cell lung cancer
Cyclin-Dependent Kinase 2 Inhibitor
PF-07104091
palbociclib
letrozole
cyclin-dependent kinase
Ibrance
Femara
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Ovarian Neoplasms
Small Cell Lung Carcinoma
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action