Studies for People with ER-Positive, HER2-Negative Advanced or Metastatic Breast Cancer (TACTIVE-U)

Researchers at Pfizer and Arvinas are conducting the TACTIVE-U studies for people with ER-positive, HER2-negative advanced or metastatic breast cancer who have received at least one prior round of treatment and no more than two prior rounds of treatments for advanced or metastatic disease. One of these rounds of treatment must have included a CDK4/6 inhibitor (e.g., Kisqali, Verzenio, Ibrance).

The TACTIVE-U studies are looking at the safety of an oral study medicine, ARV-471 (also known as vepdegestrant), and how well it works when combined with other breast cancer medicines.

ARV-471 (vepdegestrant) is believed to work by targeting and degrading the estrogen receptor that is found in breast cancer cells. This prevents estrogen from connecting to the cancer cells, which may block estrogen’s effect on cancer cell growth.

More information about the TACTIVE-U studies can be found here: https://www.pfizerclinicaltrials.com/nct05548127-or-nct05573555-advanced-and-metastatic-breast-cancer-trial

What the Studies Involve

TACTIVE-U is open-label, so participants will know the medicines and the doses of the medicines they are receiving. Medicine doses may vary across participants in order to find the best dosing options for treating advanced or metastatic breast cancer.

• Substudy B: Participants receive ARV-471 (vepdegestrant) and ribociclib (a CDK4/6 inhibitor)
• Substudy C: Participants receive ARV-471 (vepdegestrant) and samuraciclib (a CDK7 inhibitor)

There are no placebo (inactive medicine) groups in these studies

Any steps needed to screen, qualify or enroll

• In Substudy B, most participants will take ARV-471 alone and some participants will take ribociclib alone for 7 days before taking both medicines. This is called the “lead-in” period.
• In Substudy C, some participants will take samuraciclib alone on some days and ARV-471 alone on other days for 2 weeks before taking both ARV-471 and samuraciclib in combination. This is called the “drug-drug interaction assessment.”

Type of treatment, dose, frequency, duration

All studies are researching ARV-471. ARV-471 is taken by mouth once a day at the same time in the morning with food.

• Substudy B: ARV-471 in combination with ribociclib
  • Ribociclib is taken with or without food by mouth once a day. It is taken consecutively for 21 days followed by 7 days off treatment (28-day cycles).
• Substudy C: ARV-471 in combination with samuraciclib
  • Samuraciclib is taken anytime during the day with or without food.

The length of time you can expect to participate in any of these substudies depends upon a few things, including how you tolerate the medicine(s), how your cancer responds, and your personal choice.

Any additional screening, biopsies, appointments, monitoring

• Substudy B: If joining the “lead-in” part of the study, there may be two study visits during these 7 days. During the treatment period (all participants), there are three study visits during the first cycle (including two study visits in the first week), two study visits during second cycle, and study visits every 4 weeks thereafter until the end of treatment. Each cycle lasts 4 weeks. Most study visits last for about 1-2 hours. There will be some longer visits which will last up to about 8 hours.
• Substudy C: If participating in the “drug-drug interaction assessment” part of the study, there may be 4 visits (2 in the first week and 2 in the second week). During the treatment period (all participants), participants will likely attend study visits every 2 weeks for the first 2 cycles (each cycle is 4 weeks), and every 4 weeks thereafter until the end of treatment.

In all substudies, most study visits will include a physical examination, blood draws, heart monitoring, a discussion of how you are feeling, and other assessments and activities. Your tumor will be assessed every 8 weeks during the first year, and then every 12 weeks thereafter. This includes scans and measurement of skin/superficial lesions, if any. Bone scans will be carried out every 24 weeks.

Any additional follow ups or steps involved in participation and a timeline

• There is an end-of-treatment visit after your last dose of the study medicines. About one month after your last dose of study medicine, you will attend a final visit for the study team to observe your health. You might be contacted every three months to check on your health.

Any compensation they may receive for treatment-related costs

• The study medicines and any study-related procedures are generally covered at no cost. Participants may be reimbursed for any reasonable expenses that they may have as a result of taking part in the study. This may include parking, meals, or other travel-related expenses.

Study Locations:

• Substudy B: https://clinicaltrials.gov/study/NCT05573555
• Substudy C: https://clinicaltrials.gov/study/NCT06125522

Lead Researchers/Study PIs and Affiliation:

Dr. Cynthia Ma, Washington University in St. Louis, St. Louis, MO

People with the following may be eligible:

• 18 years old and older
• Have ER-positive, HER2-negative advanced or metastatic breast cancer and cannot be fully treated by surgery or radiation therapy
• Have received at least 1 prior round of treatment and no more than 2 prior rounds of treatments for advanced or metastatic disease
  • 1 (and only 1) of these rounds of treatment must have included a CDK4/6 inhibitor (e.g. Kisqali (ribociclib), Verzenio (abemaciclib), Ibrance (palbociclib))
• Their cancer is no longer responding to previous treatments

There are other requirements to join this study. The study doctor will help determine if this study is right for you.

People with the following are not eligible:

• History of any tumor malignancies other than breast cancer within the past 3 years
• Have newly diagnosed brain metastasis or symptomatic (e.g., headache, nausea, vomiting, etc.) central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease
• Have inflammatory breast cancer
• Have clinically significant heart (cardiovascular) disease
• Have kidney (renal) impairment, not adequate liver function and/or bone marrow function

There are other requirements to join this study. The study doctor will help determine if this study is right for you.