A Phase I/II Study of GVV858 Alone or in Drug Combination for Patients with Advanced Hormone Receptor‑Positive, HER2‑Negative Breast Cancer

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What is this study about?

Advanced hormone receptor positive, HER2-negative breast cancer and other advanced solid tumors are being studied. Hormone receptor positive means the cancer can grow when hormones are present, while HER2-negative means the tumor does not have extra HER2 protein. The study investigates the investigational drug GVV858, taken as a capsule by mouth, either by itself or together with standard hormone‑blocking treatments. These hormone therapies include the injectable medicine fulvestrant, the pill letrozole, and background hormone suppression with the injectable drugs leuprorelin acetate and goserelin. Hormone‑blocking treatments work by lowering hormone levels or blocking the hormones from reaching cancer cells.

The purpose of the study is to assess how safe the investigational drug is and to determine the appropriate dose when used alone or in combination with the hormone therapies.

Participants will first undergo screening tests, then begin taking the study medication in a series of visits. Depending on the study arm, they may receive an injection of the hormone blocker, a daily pill, or both, alongside the oral investigational drug. Throughout the study they will have regular check‑ups that include blood work, vital‑sign measurements, and heart rhythm checks to monitor safety. Treatment continues until the cancer shows growth, side effects become unacceptable, or the study ends.

1 baseline assessments

after joining, initial medical examinations are performed to record current health status.

tests may include blood work, vital signs, electrocardiograms, and imaging studies to establish a reference point.

2 background hormone therapy

the patient receives a subcutaneous injection of leuprorelin acetate or goserelin according to the study protocol.

the exact dose, frequency and duration are defined by the trial schedule and are administered throughout the treatment period.

3 gvv858 single‑agent administration

the patient takes oral capsules containing gvv858 as a single agent.

the capsule is taken by mouth each day as instructed; the specific dose and length of treatment follow the protocol.

4 combination with fulvestrant (if assigned)

for patients assigned to this arm, an intramuscular injection of fulvestrant is added to the regimen.

the injection is given at intervals set by the study, continuing alongside daily gvv858 capsules.

5 combination with letrozole (if assigned)

for patients assigned to this arm, oral letrozole is taken in addition to the daily gvv858 capsule.

the tablet is taken each day; the schedule follows the trial protocol.

6 regular monitoring visits

the patient attends scheduled clinic visits for safety monitoring, including laboratory tests, vital‑sign checks, and electrocardiograms.

imaging studies may be repeated to evaluate disease status according to the trial timetable.

7 treatment continuation or discontinuation

treatment is continued until disease progression, unacceptable side effects, or completion of the prescribed study period.

if any dose reductions, interruptions, or discontinuations are required, they are managed according to protocol guidelines.

Who Can Join the Study?

You must be 18 years old or older.
You must have an advanced cancer for which the doctor believes no standard treatment is suitable.
If you have HR+/HER2- advanced breast cancer, the disease must have gotten worse while you were on, or you could not tolerate, at least one hormone‑based therapy combined with a CDK4/6 inhibitor, and you must have received at least one additional line of systemic treatment for the spread of cancer.
If you have a solid tumor (such as breast, ovarian, gastric, or esophageal cancer) that is locally advanced or has spread and shows CCNE‑1 amplification (a specific genetic change), you may be eligible.
For the Phase I expansion part, you may also have advanced ovarian, gastric, or esophageal cancer with CCNE‑1 amplification that has progressed after standard therapy.
If you have metastatic castration‑resistant prostate cancer, the disease must have progressed after at least one androgen receptor pathway inhibitor (a drug that blocks male hormones) and after a taxane‑based chemotherapy, and you must have had no more than three prior systemic treatments for the spread of cancer.
For Phase II, you must have HR+/HER2- advanced breast cancer that progressed after hormone therapy combined with a CDK4/6 inhibitor, and you must have had no more than two lines of hormone therapy for advanced disease and no prior chemotherapy or antibody‑drug conjugate therapy for advanced disease.
Your cancer must be measurable according to RECIST v1.1 (a system doctors use to measure tumor size). If you have breast cancer with no measurable tumor, you need at least one mainly bone lesion that can be accurately measured over time. If you have metastatic prostate cancer with no measurable disease by PCWG3 modified RECIST, you need at least one metastatic lesion visible on a bone scan before the first day of treatment.

Who Cannot Join the Study?

You cannot join if your bone marrow (the tissue that makes blood cells) or essential organ function (how well organs like the liver and kidneys work) is not adequate.
You cannot join if you have symptoms from cancer that has spread to the brain or spinal cord, called central nervous system (CNS) metastases, and you need special local treatment or higher doses of corticosteroids (steroid medicines) within two weeks before starting the study.
You cannot join if you have symptoms from cancer affecting major internal organs, known as visceral disease, especially a serious situation called a visceral crisis.
If you have breast cancer and are currently using hormone replacement therapy, or if you are a pre‑menopausal woman or a man with breast cancer and you are unwilling or unable to take a hormone‑lowering medicine called an LHRH agonist (examples: goserelin or leuprolide) for gonadal suppression, you cannot join.
Women who can become pregnant (women of childbearing potential) who are not willing to use highly reliable birth‑control methods cannot join.
If you are pregnant or nursing (breastfeeding), you cannot join.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

Site Name	City	Country	Status
University Hospital Jena KöR	Jena	Germany

Other Sites

Site Name	City	Country
Odense University Hospital	Odense	Denmark
ASST Grande Ospedale Metropolitano Niguarda	Milan	Italy
University Hospital Olomouc	Olomouc	Czechia
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hospital Universitario 12 De Octubre	Madrid	Spain
Hyslqmem Vvyy dnzqodbh	Barcelona	Spain
Uvgvgqkffirnejrnezuxy Ehzbi Alx	Essen	Germany

Trial status

Country	Status	Recruitment Start
Czechia	Not yet recruiting	09.07.2026
Denmark	Recruiting	09.07.2026
France	Not yet recruiting	09.07.2026
Germany	Not yet recruiting	09.07.2026
Italy	Recruiting	09.07.2026
Spain	Not yet recruiting	09.07.2026

Trial locations

Investigated drugs:

Leuprorelin acetate is a medication given as a subcutaneous injection that lowers estrogen levels by stopping the ovaries from making hormones. In this trial it is used as part of the standard background treatment for hormone‑sensitive breast cancer.

Goserelin is also injected under the skin and works in the same way as leuprorelin, suppressing the body’s production of estrogen. It is included in the trial as background endocrine therapy.

Fulvestrant is an injectable drug that is given into a muscle. It works by attaching to estrogen receptors on cancer cells and breaking them down, which helps stop the growth of tumors that need estrogen to grow. In this study it is combined with the investigational drug to see if the pair works better together.

Letrozole is an oral tablet that belongs to a class of medicines called aromatase inhibitors. It lowers estrogen levels by blocking the enzyme that makes estrogen from other hormones. The trial tests letrozole together with the new drug to see if the combination is safe and effective.

GVV858 is an experimental oral capsule being studied for the first time in patients with advanced hormone‑receptor‑positive, HER2‑negative breast cancer and other solid tumors. The trial looks at how safe it is when taken alone and when combined with either fulvestrant or letrozole, and aims to find the best dose for future studies.

Investigated diseases:

Hormone receptor positive HER2 negative breast cancer

Advanced hormone receptor‑positive, HER2‑negative breast cancer – It is a type of breast cancer where the tumor cells have receptors for hormones such as estrogen or progesterone but lack excess HER2 protein. The disease usually begins as a localized tumor in the breast and can spread to nearby lymph nodes. Over time, cancer cells may grow and invade surrounding tissue. If not controlled, they can travel through the bloodstream to other parts of the body such as bone, liver, or lungs. The condition is considered advanced when it has spread beyond the breast or cannot be removed by surgery.

Trial ID:

2025-521911-38-00

Protocol code:

CGVV858A12101

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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A Phase I/II Study of GVV858 Alone or in Drug Combination for Patients with Advanced Hormone Receptor‑Positive, HER2‑Negative Breast Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?