USO 23160
A Phase 3, Randomized, Open-Label, Multicenter Study Of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib For The Treatment Of Participants With Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Not Received Any Prior Systemic Anti-Cancer Treatment For Advanced Disease (VERITAC-3)(C4891002)
Disease Types: Breast Cancer Research
Eligibility Requirements:
Inclusion Criteria 1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening. a. Female participants under 60 years of age, with cessation of regular menses for 12 consecutive months and with no other alternative medical cause, must have a FSH level within the post-menopausal level, as per local laboratory reference range. b. Pre-/peri-menopausal female participants and male participants must agree to initiate or continue an LHRH agonist as per SoA and Section 6.9.1 c. WOCBP participants and male participants must 2. Participants who are willing and able, to comply with all scheduled visits, treatment plans, laboratory tests, lifestyle considerations, and other study procedures. a. Phase 3 ONLY. Participants must provide a blood sample AND a tumor sample collected at the time of diagnosis of locally advanced/metastatic disease. If not available, a de novo biopsy is required. The sole exception is those patients with bone only disease for whom archival tumor sample at initial diagnosis is acceptable. Refer to Section 8.7 for further details. 3. Histological or cytological confirmation of BC with evidence of locoregionally advanced or metastatic disease, not amenable to surgical resection or radiation therapy with curative intent. a. Documented ER(+), defined as ER(+) ≥1% stained cells by an assay consistent with local standards, on the most recent tumor biopsy, ie, at diagnosis of recurrence or metastatic disease (Allison et al, 2020). The sole exception is those patients with bone only disease for whom ER(+) using archival tissue at initial diagnosis is acceptable. b. Documented HER2(-) tumor by either IHC or in-situ hybridization per ASCO/CAP guideline (Wolff et al, 2018). c. Participants who have bilateral BCs which are both ER(+)/HER2(-) are eligible. 4. No prior systemic anti-cancer therapy for their locoregionally advanced or metastatic disease. 5. At least 1 measurable lesion as defined by RECIST v1.1. Bone only disease:participants with only non-measurable lesions are eligible. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2Exclusion Criteria 1. Other 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. 2. Any other solid tumors within the past 3 years, except for the following: 1) adequately treated basal or squamous cell carcinoma of the skin; and 2) curatively treated in situ carcinoma of the cervix. For all other solid tumors, they must have been curatively treated and with no evidence of disease for >3 years. Participants with inflammatory BC, prior hematopoietic stem cell or bone marrow transplantation are excluded. 3. Participants with newly diagnosed brain metastasis 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, radiotherapy, stereotactic surgery), are clinically stable (including participants with residual CNS symptoms/deficits) and off enzymeinducing anticonvulsants and steroids for at least 14 days prior to randomization. 4. Participants in visceral crisis at risk of immediately life-threatening complications in the short term, including participants with massive uncontrolled effusions (pleural, pericardial & peritoneal), pulmonary lymphangitis, or liver involvement >50%. 5. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as: a. Symptomatic cardiac valve disease. Participants with mitral valve prolapse that is asymptomatic or not associated with clinically significant sequalae (eg, mitral regurgitation) are eligible. b. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease, congenital long QT syndrome, Torsade de Pointes, clinical important arrhythmias, left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade. c. Cardiac rhythm device/pacemaker. Participants with cardiac rhythm device/pacemaker must be discussed in detail with sponsor medical monitor to determine eligibility. d. QTcF >470 msec on screening ECG.
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