A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery

Browse trials for

• Breast Neoplasms 12,544

Keywords

• Early breast cancer
• Localized breast cancer
• Untreated breast cancer
• Pre-operative breast cancer
• Treatment-naïve breast cancer
• Neoadjuvant
• Estrogen receptor
• Estrogen receptor positive
• ER+
• Hormone positive
• Hormone receptor positive
• HR+
• human epidermal growth factor receptor 2 negative
• HER2-
• ARV-471
• Anastrozole
• Arimidex
• Aromatase inhibitor
• Vepdegestrant
• PF-07850327

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 152 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Lead sponsor

Arvinas Inc. is the lead sponsor of 5 studies on the registry; 2 are open to participants now.

Study arms

• Experimental
  Arm A: ARV-471 (Experimental)

  Participants received 200 mg ARV-471 (2\*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than Cycle 6 Day 18 \[C6D18\] + 14 days).

  Drug: ARV-471 · Procedure: Surgical resection of breast tumor

• Active comparator
  Arm B: Anastrozole

  Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).

  Drug: Anastrozole · Procedure: Surgical resection of breast tumor

Interventions

• DrugARV-471

  100 mg tablet

  Also known as: Vepdegestrant, PF-07850327

• DrugAnastrozole

  1 mg tablet

  Also known as: Arimidex

• ProcedureSurgical resection of breast tumor

  Surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)

Primary outcomes

1. Percent Reduction in Ki-67 Expression From Baseline to Day 15 in Tumor Biopsies

   Tumor biopsy Ki-67 expression (% of tumor cells that are positive for Ki-67) at baseline and Cycle 1 Day 15 (C1D15) was collected. Ki-67 expression was assessed by immunohistochemical staining in a central laboratory. The log-transformed Ki-67 after approximately 2 weeks of treatment as a percentage of the baseline value, ie, the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline was modelled using a generalized linear model (GLM) with both stratification factors (ie, baseline Ki-67 score and the tumor size) and treatment as co-variates. The treatment effects were back transformed into geometric means and their Confidence Intervals. The percent change, in other words, relative reduction, of Ki-67 after 2 weeks of treatment is reported as the complement of the ratio between the Ki-67 measurement from C1D15 and baseline, that is 100% × (1 - geometric mean ratio between Ki-67 at C1D15 and Ki-67 at baseline).

   Time frame: Baseline (during screening, prior to Day 1) and Day 15

Secondary outcomes

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Study Drug Discontinuation

   An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE is an AE that emerges or worsens on/after the first dose of ARV-471/Anastrozole to 30 days after the last administration of the study intervention (ie, study drug treatment or surgical resection, whichever occurs last).

   Time frame: From signing of consent to minimum of 30 days after last administration of study drug (up to approximately 6.5 months)

2. Pathologic Stage at the Time of Surgical Resection

   Local pathological assessment of the tissue from surgical resection (performed after approximately 5.5 months of treatment), at minimum, included pathologic stage (ypT and ypN stage) as described in the Laboratory Manual. Participants were analysed based on the current American Joint Committee on Cancer (AJCC) staging system as follows: * Pathologic Tumor - post-neoadjuvant therapy pathologic tumor categorization (ypT): (ypTx, ypT0, ypTis, ypT1mi, ypT1a, ypT1b, ypT1c, ypT2, ypT3, ypT4a, ypT4b, ypT4c). * Pathological Lymph Nodes - post-neoadjuvant therapy pathologic node categorization (ypN): (ypNX, ypN0, ypN0(i+), ypN0(mol+), ypN1, ypN1mi, ypN1a, ypN1b, ypN1c, ypN2, ypN2a, ypN2b, ypN3, ypN3a, ypN3b, ypN3c). * ypT0 / ypN0 indicates no evidence of disease and the progressive grades indicate increasing size of tumor and increasing area of lymph node involvement respectively and ypTx/ypNX indicates non-measurable disease.

   Time frame: At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days

3. Pathological Complete Response(pCR) Rate at the Time of Surgical Resection

   pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes following completion of neoadjuvant systemic therapy (ie, Pathologic Tumor - ypT = ypT0 or ypTis, and Pathologic Lymph Nodes - ypN = ypN0 in the current American Joint Committee on Cancer (AJCC) staging system). pCR rate is the percentage of participants with pCR.

   Time frame: At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days

4. Number of Participants With Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0 at the Time of Surgical Resection

   Modified Pre-operative Endocrine Prognostic Index (mPEPI) score is an investigational prognostic tool used to predict the risk of breast cancer recurrence. It will be derived from factors assigned a numerical score following Neoadjuvant endocrine treatment (NET). The factors include pathologic tumor size, and lymph node status and Ki67 expression in the surgical specimen. Total mPEPI score (mPEPI\_T) per participant is the sum of mPEPI score of each factor. mPEPI score of 0 indicates Pathological tumor size T1-T2, no lymph nodes and Ki67 level of 0%-2.7%, 1 indicates: Ki67 level \>2.7%-7.3%, 2 indicates Ki67 level \>19.7%-53.1% and 3 indicates: tumor sizeT3-T4, presence of lymph nodes and Ki67 level \>53.1%.

   Time frame: At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days

5. Breast Conserving Surgery (BCS) Rate

   Breast conserving surgery (BCS) Rate is the percentage of participants received breast conserving surgery.

   Time frame: At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days

6. Radiographic Response Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Primary Tumor During Cycle 6

   The number of participants with Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE) per mRECIST calculated. CR = disappearance of all target lesions, PR is \>=30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>=20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

   Time frame: At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days

7. Percentage Change From Baseline at Cycle 6 Day 1 in Caliper Measurement of the Primary Tumor

   The percentage change from the baseline of the primary breast tumor size in physical exam calculated in caliper measurement. Caliper-based response is the maximum percentage decrease or minimum percentage increase if there is no decrease per participant.

   Time frame: Baseline (Day 1) and Cycle 6 Day 1 (At Day 141), each cycle is 28 days

Baseline characteristics

Study documents

• Study protocol · Jan 9, 2023
• Statistical analysis plan · Nov 15, 2024

Documents are hosted by the registry — open the source record to download them.