Phase I/IIa 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

Study Identifier:
C4161001
CT.gov Identifier:
NCT04553133
EudraCT Identifier:
2022-001679-15
EU Trial (CTIS) Number:
2024-515492-34-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To assess the safety, pharmacokinetics, pharmacodynamics and tolerability of increasing doses of PF-07104091 in patients with small cell lung, non small cell lung ovarian and breast cancers.

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

To study the safety, dose, side effects and anti-cancer activity of giving the experimental targeted therapy PF-07104091 alone, in combination with palbociclib (Ibrance®), or in combination with palbociclib and letrozole.

To determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Small Cell Lung
  • Ovarian
  • Breast Cancers
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: xperimental: PF-07104091
    • Read More
  • Drug: Experimental: PF-07104091 + palbociclib + fulvestrant
  • Drug: Experimental: PF-07104091 + palbociclib + letrozole
  • Drug: Experimental: PF-07104091 monotherapy dose expansion (SCLC)
  • Drug: Experimental: PF-07104091 monotherapy dose expansion (ovarian)
  • Drug: Experimental: PF-07104091 monotherapy dose expansion (TNBC)
  • Drug: Experimental: PF-07104091 + palbociclib + fulvestrant (post CDK4/6)
  • Drug: Experimental: PF-07104091 + palbociclib + fulvestrant (CDK4/6 naive)
  • Drug: Experimental: PF-07104091 + palbociclib + letrozole (CDK4/6 naive)
  • Drug: The end of the study is defined as the date of the last visit of the last participant in the study. The maximum duration of the trial will be approximately 2 years after last participant first dose. The study may also be terminated at any time at the discretion of the Sponsor.
  • Drug: PF-07104091 (75-500 mg) was given twice daily (BID) orally in 28-day cycles, following Bayesian design with overdose control
  • Drug: Dosage form: Tablet
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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 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
    • 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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Manish Sharma
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Small Cell Lung
    Ovarian
    Breast Cancers