A Phase IB/II, Open-label, Multicenter, Dose escalation and Dose expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PF-07220060 in Combination with PF-07104091 Plus Endocrine Therapy in Participants with Advanced Solid Tumors

Study Identifier:
C4391002
CT.gov Identifier:
NCT05262400
EudraCT Identifier:
2022-002173-28
EU Trial (CTIS) Number:
2023-509504-15-00
Study Contact Information:
N/A
Recruitment Complete

Considering participating in a START clinical trial?

Get Started

Study Summary

To assess the safety and tolerability of increasing doses of PF-07220060 in combination with PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended dose for expansion (RDE) for PF-07220060 in combination with PF-07104091 in participants with breast cancers or solid tumors and to assess the safety and tolerability of the RDE of PF-07220060 and PF-07104091 in combination with Endocrine Therapy in participants with breast cancer.

To present dose escalation multicenter data of PF-07220060 (PF-60, CDK4-selective inhibitor) plus PF-07104091 (PF-91, CDK2-selective inhibitor) in patients (pts) with HR+ HER2- metastatic breast cancer (mBC) and advanced solid tumors (NCT05262400).

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.
  • Breast Cancers
  • Solid Tumor
    • 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: Arm 1:
    • Read More
  • Drug: Arm 2:
  • Drug: Arm 3:
  • Drug: Arm 4:
  • Drug: Arm 5:
  • Drug: Arm 6:
  • Drug: Arm 7:
  • Drug: Arm 8:
  • Drug: Experimental: Part 1 Dose Escalation - Dose Level 6
  • Drug: PF-07104091
  • Drug: PF-07220060
  • Drug: Fulvestrant
  • Drug: Letrozole
  • Drug: ESMO 2024:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Part 1: Breast Cancer (BC)
    • HR+, HER2- BC
    • Refractory HR-positive/HER2-positive BC
    • Part 1: Solid Tumors other than BC
    • Part 2:
    • HR-positive/HER2-negative BC
    • Lesion:
    • Part 1: evaluable lesion (including skin or bone lesion only)
    • Part 2: measurable lesion per RECIST v1.1
    • Prior systemic Treatment
    • Part 1: HR-positive/HER2-negative BC
    • At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease.
    • Prior chemotherapy in the metastatic setting is allowed.
    • Part 1: HR-positive/HER2-positive BC
    • At least 1 prior treatment of approved HER2 targeting therapy.
    • Part 1: Solid Tumors other than BC
    • Participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator.
    • Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET.
    • Parts 2B: At least 1 prior endocrine therapy for advanced or metastatic disease. Progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable.
    • Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed.
    • General Inclusion Criteria
    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
    • Adequate renal, liver, and bone marrow function
    • Resolved acute effects of any prior therapy to baseline severity
    • Male and female participants ≥18 years of age at Visit 1.
    • Histological or cytological diagnosis of locally advanced or metastatic solid tumor/diagnosis which is unresectable.
    • Evaluable lesion (including skin or bone lesion only, Part 1)
    • Participants entering the study in the expansion cohort have at least 1 measurable lesion as defined by RECIST (version 1.1) that has not been previously irradiated.\
    • Cancer type:
    • HR-positive HER2-negative tumor (Part 1 and Part 2)
    • HR-positive HER2-positive tumor (Part 1)
    • Advanced solid tumor or metastatic disease (Part 1)
    • ECOG PS 0 or 1.
    Exclusion criteria
    • All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.
    • Part 2B and 1C: Prior treatment with any CDK 4/6 inhibitor, or SERDs (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway for advanced disease.
    • Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.
    • Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.
    • Part 2C: Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
    • Part 2C: Any prior systemic treatment for advanced disease.
    • Prior irradiation to >25% of the bone marrow
    • Current use of drugs which have a risk for QTc prolongation
    • Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers
    • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
    • Participants with any other active malignancy within 3 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease
    • Major surgery within 4 weeks prior to study entry
    • Radiation therapy within 4 weeks prior to study entry.
    • Clinically important hypertension
    • Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)
    • Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed
    • Known active uncontrolled or symptomatic central nervous system (CNS) metastases
    • Active inflammatory GI disease
    • Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention
    • Previous high-dose chemotherapy requiring stem cell rescue
    • Participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
    • Other protocol specific exclusion criteria may apply
    • Prior/concomitant treatment as follows:
    • prior treatment with any CDK 4/6 inhibitor, or fulvestrant, or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway (Part 2B);
    • prior neoadjuvant or adjuvant treatment with a non-steroidal AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment (Part 2C);
    • prior treatment with any CDK4/6 inhibitor for advanced disease (Part 2B and 2C);
    • radiation therapy within 4 weeks prior to study enrollment, with the exception of palliative radiotherapy following discussion with the sponsor.
    • Inadequate organ function.
    • Known bleeding disorders.
    • Participation in other studies involving investigational drug(s) within 4 weeks (or 5 half-lives, whichever is shorter) prior to study entry.Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen’s disease.
    • Current use or anticipated need for PPI within 14 days prior to first dose of the study intervention. For participants with gastroesophageal reflux disease, concurrent treatment with PPIs is not allowed and treatment with H2 blockers and/or antacids if medically required must be dosed according to protocol guidelines.
    • Previous high-dose chemotherapy requiring stem cell rescue.
    • Last anticancer treatment within 2 weeks (or 5 half-lives, whichever is shorter, unless the last immediate anticancer treatment contained an antibody-based agent(s) (approved or investigational), then the interval of 4 weeks or 5 half-lives (whichever is shorter) is required prior to receiving the study intervention (except in Part 2C where no systemic anticancer treatment in advanced or metastatic setting is allowed).

    Clinical Study Information for Healthcare Providers

    By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

    View Study Information

    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Manish Sharma
    Status
    Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Solid Tumor
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Ramon Yarza
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Solid Tumor