A Study Comparing GDC-4198 Alone and with Giredestrant versus Abemaciclib with Giredestrant for Advanced Breast Cancer After Previous CDK4/6 Treatment

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What is this study about?

This study involves people with breast cancer that is estrogen receptor-positive and HER2-negative, meaning the cancer cells have receptors for the hormone estrogen but do not have high levels of a protein called HER2. The cancer has either spread to other parts of the body or has grown locally in a way that cannot be treated with surgery or radiation aimed at curing the disease. All participants in this study have already received treatment with a type of medicine called a CDK4/6 inhibitor, which works by blocking certain proteins that help cancer cells grow, but their cancer has continued to grow or spread despite this treatment. The study will test several medicines given by mouth: GDC-4198, which is also known as RO7840734, giredestrant, which is also known as RO7197597, and abemaciclib. GDC-4198 is a new type of CDK4/6 inhibitor, while giredestrant works by blocking estrogen receptors on cancer cells, and abemaciclib is an already approved CDK4/6 inhibitor.

The purpose of this study is to find out if GDC-4198 is safe when given alone or together with giredestrant, and to compare how well GDC-4198 combined with giredestrant works against cancer compared to abemaciclib combined with giredestrant. The study will also look at how the body processes these medicines and how they affect the cancer. The study is divided into two stages. In the first stage, a small number of participants will receive GDC-4198 either alone or with giredestrant to check for safety and to understand how the body handles the medicine. In the second stage, a larger number of participants will be randomly assigned to receive either one of two different doses of GDC-4198 combined with giredestrant, or abemaciclib combined with giredestrant. Throughout the study, doctors will monitor participants closely with regular check-ups, blood tests, and scans to see how the cancer responds to treatment and to watch for any side effects.

During the study, doctors will measure several things to understand how well the treatments work and how safe they are. They will check how long it takes before the cancer starts growing again, whether the cancer shrinks or disappears, and how long any improvement lasts. They will also track any unwanted effects from the medicines, changes in vital signs like blood pressure and heart rate, and results from blood tests. The study will also measure the levels of the medicines in the blood at different times to understand how the body processes them. Some participants will receive GDC-4198 with and without food to see if eating affects how the medicine works. The study will continue for several years to gather enough information about the long-term effects of these treatments.

1 Initial treatment assignment

Upon joining the study, you will be assigned to one of the treatment groups. This assignment will be done randomly, similar to flipping a coin.

The study has two main stages: Phase Ib Stage and Phase II Stage. The stage you participate in will determine which treatment combination you receive.

2 Treatment administration

You will receive medication by mouth in the form of hard capsules.

Depending on your assigned group, you may receive one of the following treatment combinations:

– GDC-4198 alone

– GDC-4198 in combination with giredestrant

– Abemaciclib in combination with giredestrant

All medications are taken orally. The specific dose levels and frequency will be determined by the study protocol and your assigned treatment group.

3 Regular monitoring visits

Throughout the study, you will attend regular monitoring visits.

During these visits, your vital signs will be measured. Vital signs include basic body measurements such as blood pressure, heart rate, and temperature.

Blood samples will be collected for clinical laboratory tests to monitor how your body is responding to the treatment.

These tests will help track any changes from your initial baseline measurements taken at the start of the study.

4 Safety assessments

Your health and safety will be monitored continuously during the study.

Any side effects or unwanted reactions to the medication, called adverse events, will be recorded and assessed.

The severity of any adverse events will be evaluated using a standardized grading system.

In the early phase of the study, specific attention will be given to identifying dose-limiting toxicities, which are serious side effects that may require dose adjustments.

5 Disease monitoring

Your cancer will be monitored regularly to see how it responds to the treatment.

This monitoring will assess whether the cancer has grown, shrunk, or remained stable.

The measurements will be done according to standardized criteria called RECIST v1.1, which is a system used to evaluate tumor response in solid cancers.

The study will track progression-free survival, which measures the length of time during and after treatment that you live without the cancer getting worse.

6 Pharmacokinetic assessments

Blood samples will be collected at specific times to measure the levels of the study medication in your bloodstream.

These measurements help understand how your body processes the medication, including how it is absorbed, distributed, and eliminated.

For participants receiving GDC-4198, samples will be taken both when you have not eaten (fasted condition) and after eating (fed condition) to see if food affects how the medication works.

The study will also measure any breakdown products of the medication, called metabolites, that form in your body.

7 Ongoing treatment period

You will continue taking your assigned medication as long as it is providing benefit and you are not experiencing unacceptable side effects.

The study is expected to continue until August 2028, though your individual participation may be shorter or longer depending on how you respond to treatment.

Throughout this period, all monitoring activities, including safety assessments, disease evaluations, and blood sample collections, will continue at scheduled intervals.

Who Can Join the Study?

You must have a confirmed diagnosis of breast cancer that is adenocarcinoma (a type of cancer that starts in gland cells). This diagnosis must be confirmed through histology (examination of tissue under a microscope) or cytology (examination of cells under a microscope). Your cancer must be locally advanced (cancer has spread to nearby tissues and cannot be removed by surgery or treated with radiation to cure it) or metastatic (cancer has spread to other parts of the body).
Your tumor must be estrogen receptor-positive (also called ER+), which means the cancer cells have receptors that allow estrogen to attach to them and help them grow. This must have been confirmed in previous testing according to recognized medical guidelines.
Your tumor must be HER2-negative (also called HER2–), which means the cancer cells do not have too much of a protein called human epidermal growth factor receptor 2. This must have been confirmed in previous testing according to recognized medical guidelines.
Your cancer must have gotten worse during or after treatment with a CDK4/6 inhibitor (a type of medicine that blocks proteins that help cancer cells grow, such as abemaciclib, palbociclib, or ribociclib) combined with endocrine therapy (hormone therapy) when your cancer was locally advanced or metastatic.
You must have disease that can be measured or evaluated according to standard cancer response criteria called RECIST v1.1 (a system doctors use to measure tumors and track if they are growing, shrinking, or staying the same).
You must have an ECOG Performance Status of 0 or 1. This is a scale that measures how well you can perform daily activities. A score of 0 means you are fully active and able to do all activities as before your illness. A score of 1 means you cannot do physically demanding activities but can do light work or activities.

Who Cannot Join the Study?

You have brain metastases (cancer that has spread to the brain) that are not stable or controlled
You have other types of cancer within the last 3 years, except for certain low-risk skin cancers or cancers that were completely removed
You have received certain previous cancer treatments, including specific types of chemotherapy (strong medicines that kill cancer cells) or targeted therapy (medicines that attack specific cancer cells) within a set time period before joining the study
You have severe or uncontrolled medical conditions such as heart disease, lung disease, or active infections
You have abnormal blood test results showing that your bone marrow (the tissue inside bones that makes blood cells) is not working properly
You have abnormal liver or kidney function tests showing these organs are not working well enough
You have a history of certain heart problems, including abnormal heart rhythm (irregular heartbeat) or other heart conditions that could be made worse by the study treatment
You are pregnant, breastfeeding, or planning to become pregnant during the study
You have known allergies or severe reactions to the study medicines or similar medications
You are taking certain other medications that could interfere with the study treatment
You have had major surgery within a certain time period before starting the study
You have difficulty swallowing pills or have digestive problems that would prevent you from absorbing the study medication properly

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut Gustave Roussy	Villejuif	France
Technische Universitaet Dresden	Dresden	Germany
Medizinische Hochschule Hannover	Hanover	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Institut Godinot	Reims	France
Universitaetsklinikum Tuebingen AöR	Tuebingen	Germany
Ospedale San Raffaele S.r.l.	Milan	Italy
Universita Degli Studi Di Brescia	Brescia	Italy
Centre Francois Baclesse	Caen	France
Centre De Lutte Contre Le Cancer Eugene Marquis	Rennes	France
Uzppnxnxko Mmimgoh Cwxicc Hjkzparidootmdtwv	Hamburg	Germany
Iptqokds Cjyqmx Ddzccaofamlelgmfc	L'hospitalet De Llobregat	Spain
Ifozlomc Rofobndmb Pmm Lg Seknyi Dhs Tukugy Dfnp Aqvcidi Ieag Sbhdrs	Meldola	Italy
Arkttqn Uejlh Stcjakcbg Lvtojn Dw Bgdoiih	Bologna	Italy
Ascucbh Olumjrjxpyl Pqdv Gfrrfizl Xyula	Bergamo	Italy
Kjoqilxu Eoqnkcsdgzmjnfdpudcgpmsn Hjgwmzleizcytoqyd	Essen	Germany
Hwjwkqro Vwab dabyhwvy	Barcelona	Spain
Cgbotl Owqyc Lcgdbif	Lille	France

Trial status

Country	Status	Recruitment Start
France	Recruiting	20.12.2025
Germany	Recruiting	20.12.2025
Italy	Recruiting	20.12.2025
Spain	Recruiting	20.12.2025

Trial locations

Investigated drugs:

GDC-4198 is an investigational medication being studied for the treatment of breast cancer. In this trial, it is being tested both on its own and when combined with other medications to see how well it works and how safe it is for patients whose cancer has continued to grow despite previous treatment.

Giredestrant is a medication that works by blocking estrogen receptors in the body. Estrogen is a hormone that can help certain breast cancers grow, so blocking its effects may help slow or stop the cancer from growing. In this trial, it is being used in combination with other medications.

Abemaciclib is an approved cancer medication that works by blocking certain proteins called CDK4 and CDK6, which help cancer cells grow and divide. By blocking these proteins, the medication may help slow down or stop the growth of cancer cells. In this trial, it is being used in combination with giredestrant as a comparison treatment.

Investigated diseases:

Estrogen Receptor-Positive Breast Cancer – This is a type of breast cancer where the cancer cells have receptors that bind to the hormone estrogen, which helps the cancer grow. The presence of these receptors means that estrogen is fueling the growth of the tumor. This form of breast cancer is one of the most common types, accounting for a significant portion of all breast cancer cases. The cancer cells multiply when they come into contact with estrogen in the body. Over time, if left unaddressed, the cancer can spread from the breast tissue to nearby lymph nodes and other parts of the body. The progression depends on various factors including the specific characteristics of the cancer cells and how quickly they divide.

Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer – This type of breast cancer is characterized by the absence or low levels of a protein called HER2 on the surface of cancer cells. HER2 is a protein that can promote the growth of cancer cells when present in high amounts. In HER2-negative breast cancer, the cancer cells do not have an overexpression of this protein, which affects how the disease behaves and develops. These cancers typically grow at a different rate compared to HER2-positive cancers. The cancer begins in the breast tissue and can progress locally within the breast or spread to other areas of the body over time.

Locally Advanced Breast Cancer – This refers to breast cancer that has grown considerably within the breast or has spread to nearby tissues and lymph nodes, but has not yet spread to distant parts of the body. The tumor may be large in size or may have extended into the chest wall or skin of the breast. Lymph nodes near the breast, such as those under the arm or near the collarbone, may contain cancer cells. The cancer is more extensive than early-stage disease but is still confined to the breast region and nearby structures. As it progresses, the tumor continues to grow locally and may involve more surrounding tissue.

Metastatic Breast Cancer – This is breast cancer that has spread from the breast to distant parts of the body through the bloodstream or lymphatic system. Common sites where breast cancer may spread include the bones, lungs, liver, and brain. The cancer cells break away from the original tumor in the breast and travel to other organs where they form new tumors. This represents an advanced stage of breast cancer where the disease is no longer confined to the breast area. The cancer continues to grow in these distant locations, affecting the function of the organs involved. The progression involves the ongoing growth and potential spread to additional sites in the body.

Trial ID:

2025-521128-31-00

Protocol code:

GO46021

Trial Phase:

Human Pharmacology (Phase I) – Other

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A Study Comparing GDC-4198 Alone and with Giredestrant versus Abemaciclib with Giredestrant for Advanced Breast Cancer After Previous CDK4/6 Treatment

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?