IRB Study Number 25-747
Status Recruiting
Phase Phase 3
Location Cleveland Clinic Weston Hospital
Institute Taussig Cancer Institute
Description
Aim 1:
To compare the efficacy of PF-07220060 in combination with letrozole (Arm A) versus CDK4/6i (investigator’s choice: abemaciclib, palbociclib, or ribociclib) in combination with letrozole (Arm B) with respect to Progression Free Survival.
Aim 2:
To compare Arm A versus Arm B with respect to overall survival (OS).
Aim 3:
To compare safety and tolerability between Arm A and Arm B.
Inclusion Criteria
- 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening.
- Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Pregnant or breastfeeding females, as well as WOCBP or males unwilling or unable to follow the contraception requirements, are not eligible for the study.
- Pre/perimenopausal female and male participants must receive therapy with an LHRH agonist prior to the first dose of study intervention (if not already ongoing) and continue throughout the study as outlined in the SoA and Section 6.9.1.1.
- Histological confirmation of BC with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
- Documented ER positive and/or PR positive tumor (as assessed locally), defined as ≥1% ER-positive and/or PR-positive stained cells utilizing an assay consistent with local standards, on the most recent tumor biopsy report, preferably in a/mBC. Although not required as a protocol procedure, de novo biopsy for a/mBC should be considered if there is no prior biopsy in this setting.
- Documented HER2-negative tumor by either IHC or in situ hybridization per ASCO/CAP guidelines (Wolff et al, 2023).
Previously untreated with any systemic anticancer therapy for their locally advanced or metastatic disease. Note: Patients who have received ≤2 weeks of NSAI in this disease setting immediately preceding screening and agree to discontinue NSAI until study treatment initiation may participate.
Resolution of acute effects of any prior therapy to no worse than CTCAE Grade 1 (except for AEs not constituting a safety risk in the investigator’s judgment).
Participants must have either measurable disease or non-measurable bone only disease. Measurable and non-measurable disease are defined by RECIST v1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented. Non-measurable bone-only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component.
Participants must have an ECOG PS of ≤2.
Exclusion Criteria
Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or Bowen’s disease. Participants with a history of other curatively treated cancers within 3 years prior to enrollment must be discussed with the sponsor prior to entering the study.
Known or suspected hypersensitivity to active ingredient/excipients of PF-07220060 or other study interventions.
Participants in visceral crisis at risk of immediately life-threatening complications in the short term, including participants with massive uncontrolled effusions (pleural, pericardial, and peritoneal), pulmonary lymphangitis, or liver involvement >50%.
Current or past history of CNS metastases.
Unable to swallow oral medication without crushing, dissolving, or chewing tablets.
Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s). Refer to Section 6.9.
Have received PF-07220060 or other investigational anticancer treatments in any setting.
Have received prior (neo)adjuvant ET and had recurrence during or within 12 months after the last dose of ET.
Have received prior (neo)adjuvant CDK4/6i and had recurrence during or within 12 months after the last dose of CDK4/6i.
Major surgery or radiation within 2 weeks of randomization or has not recovered from major side effects.
Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
QTcF interval >480 ms or history of prolonged QT syndrome.
Renal impairment as defined as an eGFR <45 mL/min/1.73 mEPI equation.
Hepatic dysfunction defined as:
- Total bilirubin >1.5 × ULN (except for Gilbert’s syULN and/or direct bilirubin >1.5 × ULN is exclusionary)
- AST >3 × ULN (>5 × ULN if attributed to liver metastases)
- ALT >3 × ULN (>5 × ULN if attributed to liver metastases)
- Alkaline phosphatase >2.5x ULN (>5x ULN in case of metastasis)
- Hematologic abnormalities defined as:
- ANC < 1,500/mm3
-Platelets < 100,000/mm3 - Hemoglobin < 9 g/dL
- Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
