AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH PF-07220060 IN PARTICIPANTS AGED 18 YEARS AND OLDER WITH ER+/HER2- ADVANCED OR METASTATIC BREAST CANCER
- Conditions
- ADVANCED OR METASTATIC BREAST CANCERMedDRA version: 21.1Level: LLTClassification code: 10072737Term: Advanced breast cancer Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508130-33-00
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 65
Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening., 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 immunohistochemistry (IHC) or in-situ hybridization per ASCO/CAP). -Participants who have bilateral breast cancers that are both ER+/HER2- are eligible. -Tumor block collected at the time of diagnosis with local recurrent or metastatic disease or archival tumor tissue is required for inclusion (Phase 1b and Phase 2)., Prior anticancer therapies, Phase 1b: Participants should have received at least 1 line of standard of care (SOC) for A/MBC. ; Prior fulvestrant allowed. ; =1 prior chemotherapy line (no antibody-drug conjugates permitted) for A/MBC setting allowed., Prior anticancer therapies; Phase 2: At least one and maximum 2 lines of endocrine therapy (ET) in A/MBC setting and most recent ET-based regimen for >6 months.; 1, and only 1, prior CDK4/6 inhibitor, inhibitor-based regimen required (independent of the setting eg, adjuvant or advanced/metastatic). ; Up to 1 prior regimen of cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting. ; Prior fulvestrant allowed., Lesions at study entry; Phase 1b:Participant with only non-measurable lesion (including skin or bone lesion only) are eligible., Lesions at study entry; Phase 2: Participants must have at least 1 measurable lesion as defined by RECIST v1.1. Participants with bone lesions only can be included if at least one bone lesion has a measurable component as for RECIST v1.1., Eastern Cooperative Oncology Group (ECOG) performance status (PS) at study entry: Phase 1b: -ECOG PS 0 or 1. Phase 2: -ECOG PS =2.
Participants in visceral crisis at risk of life-threatening complications in the short term, including participants with massive uncontrolled effusions (pleural, pericardial, and/or peritoneal), pulmonary lymphangitis, and liver involvement >50%., Concurrent administration of medications, food, or herb supplements that are strong inhibitors /inducers of cytochrome P (CYP)3A or UGT2B7, moderate inducers of CYP3A (Phase 1b only), and drugs known to predispose to Torsade de Pointes or QT interval prolongation. Prior use of strong inhibitors of CYP3A or UGT2B7 must be stopped 7 days, strong inducers of CYP3A or UGT2B7, and moderate inducers of CYP3A (Phase 1b only) must be stopped 14 days before enrollment in the study., Renal impairment defined by an estimated Glomerular Filtration Rate (eGFR) <50 mL/min/. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately., Hepatic dysfunction defined as: -Total bilirubin >1.5 × upper limit of normal (ULN) unless the participant has documented Gilbert’s syndrome (in this case total bilirubin =3 × ULN); -Aspartate aminotransferase (AST) >3 × ULN (>5 × ULN if attributed to liver metastases); -Alanine aminotransferase (ALT) >3 × ULN (>5 × ULN if attributed to liver metastases); -Alkaline phosphatase >2.5 × ULN or >5 x ULN if liver or bone metastases present.; -aPTT >1.25 × ULN and international normalized ratio (INR) >1.25 unless the participant is receiving anticoagulation, then activated partial thromboplastin time (aPTT) and INR should be within the therapeutic range of the intended use., Hematologic abnormalities defined as: -Absolute neutrophil count (ANC) < 1,500/mm3 or 1.5 × 109/L; -Platelets <100,000/mm3 or 100 × 109/L; -Hemoglobin <9 g/dL. Receipt of a blood transfusion (blood or blood products) within 14 days before the first dose is allowed., Known active infection including hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness (screening for chronic conditions is not required). A participant who has a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is known to have asymptomatic infection, or is suspected of having SARS-CoV-2, is not eligible for the study, except in case SARS-CoV-2 infection occurring during the screening period is resolved at least 14 days prior to enrollment. Note: active viral hepatitis infection is defined as untreated/uncontrolled hepatitis (eg, hepatitis B patients who are treated and whose liver function tests (LFTs) meet eligibility are not considered to have active hepatitis B). For HIV infection, the study participant is eligible if the disease is controlled with treatment, and the therapy does not exclude the participant as per Exclusion criterion., 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., Participants with newly diagnosed brain metastases, or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiother
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method