An open-label, interventional, Phase Ib/II safety and efficacy study evaluating the tolerability, PK, and antitumor activity of the oral proteolysis-targeted chimeric Vepdegestrant (ARV-471/PF-07850327) in combination with PF-07220060 in participants aged 18 years and older with ER+/HER2- advanced or metastatic breast cancer
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Study Summary
The purpose of this study is to learn about the safety and effects of giving vepdegestrant along with PF-07220060. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat. The study is seeking for participants who have breast cancer that:
- is hard to treat (advanced) and may have spread to other organs (metastatic).
- is sensitive to hormonal therapy (it is called estrogen receptor positive).
- is no longer responding to treatments taken before starting this study.
All the participants will receive vepdegestrant and PF-07220060. Both medicines will be taken by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicines are safe and effective. Participants will continue to take vepdegestrant and PF-07220060 until:
- their cancer is no longer responding, or
- side effects become too severe. They will have visits at the study clinic about every 4 weeks.
To evaluate the combination of vepdegestrant + PF-07220060 in pts ≥18 y with confirmed ER+/HER2- advanced breast cancer.
The phase 1b portion will use an escalation/de-escalation approach to determine the recommended phase 2 dose (RP2D) of the combination of vepdegestrant and PF-07220060.
The phase 2 portion will further evaluate the preliminary antitumor activity, safety, and pharmacokinetics (PK) of the combination at the RP2D. Pts (N≈65) will receive vepdegestrant orally once daily continuously and PF-07220060 orally twice daily continuously.
- - Histological or cytological diagnosis of breast cancer. At time of enrollment this
- must not be amenable to surgical resection with curative intent (≥1% ER+ stained cells
- as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ
- hybridization per ASCO/CAP).
- - prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Prior
- fulvestrant allowed; ≤1 prior chemotherapy line (no antibody-drug conjugates
- permitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines of ET
- in A/MBC setting and most recent ET-based regimen for >6 months.
- 1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimen of
- cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting;
- Prior fulvestrant allowed.
- - Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion
- as defined by RECIST v1.1. (Phase2) are eligible.
- - ECOG PS = 0 or 1 (Phase1b) ; ≤2 (Phase2)
- - visceral crisis at risk of life-threatening complications in the short term.
- - Any condition precluding an adeguate absorption of study interventions.
- - newly diagnosed brain metastases, or symptomatic central nervous system (CNS)
- metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a
- history of CNS metastases or cord compression are eligible if they have been
- definitively treated, clinically stable and discontinued anti-seizure medications and
- corticosteroids for at least 28 days prior to enrollment in the of study.
- - history of any other tumor malignancies within the past 3 years, except for the
- following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2)
- curatively treated in situ carcinoma of the cervix. Inflammatory breast cancer are
- excluded
- - impaired cardiovascular function or clinically significant cardiovascular diseases.
- - concurrent administration of medications, food, or herb supplements that are strong
- inhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only) and
- drugs known to predispose to Torsade de Pointes or QT interval prolongation.
- - renal impairment, not adequate liver function and/or bone marrow function.
- - known active infection
Clinical Study Information for Healthcare Providers
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