Evaluation of Safety and Efficacy of MK-2870 and Paclitaxel in Second-Line Treatment of Advanced/Metastatic Gastroesophageal Adenocarcinoma

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What is this study about?

This clinical trial is focused on studying treatments for advanced gastroesophageal cancer, which includes cancers of the stomach and the area where the stomach meets the esophagus. The study is exploring the safety and effectiveness of a combination of medications, including MK-2870 and paclitaxel, as a second-line treatment. Second-line treatment refers to the therapy given when initial treatment (first-line) does not work or stops working. MK-2870 is a new investigational drug, while paclitaxel is a chemotherapy medication commonly used to treat various types of cancer.

The purpose of this study is to evaluate how safe and tolerable the combination of MK-2870 and chemotherapy is for patients. The study will also look at how well the treatment works in shrinking or controlling the cancer. Participants will receive the study medications through an intravenous infusion, which means the drugs are given directly into a vein. The study will monitor participants for any side effects and measure how the cancer responds to the treatment over time.

In addition to MK-2870 and paclitaxel, the study may involve other medications such as buclizine hydrochloride, paracetamol (also known as acetaminophen), codeine phosphate, ramucirumab, and glucocorticoids. These medications may be used to manage symptoms or side effects. The study aims to provide valuable information on the potential benefits and risks of these combination therapies for patients with advanced gastroesophageal cancer.

1 study treatment begins

After you join the study, you start one of the assigned treatment combinations for advanced gastroesophageal adenocarcinoma (a cancer of the area where the food pipe meets the stomach, or the stomach itself). The study is open-label, which means that the treatment given is known and is not hidden.

The study includes different treatment groups. The listed medicines are paclitaxel given by intravenous infusion (medicine given into a vein), ramucirumab given by intravenous infusion, MK-2870 (sacituzumab tirumotecan) given as a solution for injection, and MK-1022 (patritumab deruxtecan) given as a solution for intravenous infusion.

Some medicines are also listed as background treatment: glucocorticoids (a type of steroid medicine), an H2-receptor antagonist (a medicine that reduces stomach acid), antihistamines (medicine used to reduce allergic reactions), and paracetamol taken by mouth. The source data do not give the dose, frequency, or duration for these medicines.

2 safety lead-in phase

During the safety lead-in phase, your treatment is checked for safety and tolerability. This means the study team looks for side effects and decides whether the treatment combination can be given safely.

The main safety measures are whether you develop a dose-limiting toxicity (a side effect severe enough to limit treatment), whether you have any adverse event (a medical problem that happens during the study), and whether you stop the study treatment because of an adverse event.

No dose, frequency, or exact treatment length is provided in the source data for the medicines used in this phase.

3 efficacy phase

If you continue in the study, the next part checks how well the treatment works. The study measures the objective response rate (ORR), which means the percentage of participants whose cancer gets smaller or disappears on scans.

The study also measures progression-free survival (PFS), which is the time during which the cancer does not get worse; duration of response (DOR), which is how long a response lasts; and overall survival (OS), which is how long participants live after starting treatment.

During this phase, the study also records the percentage of participants who have an adverse event or stop study treatment because of an adverse event. The source data do not provide the dose, frequency, or duration of the medicines.

4 antibody testing and follow-up assessments

The study checks for anti-drug antibodies (ADAs), which are proteins your body may make against a study medicine. This is listed for sacituzumab tirumotecan and patritumab deruxtecan.

The study period continues with assessment of safety and cancer response through the trial stages. The source data do not provide any additional trial steps, medication schedules, or exact treatment duration beyond the overall study dates.

Who Can Join the Study?

Have a confirmed diagnosis by tissue or cell testing of one of the following: stomach adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma that has been treated before and is now in the second line of treatment, meaning it has already received a first treatment and needs another one.
Have metastatic disease, meaning the cancer has spread, or locally advanced, unresectable disease, meaning the cancer has grown too much to be removed by surgery.
Have clear proof that the cancer got worse, seen on scans or by medical examination, during or after first-line treatment that included a platinum drug and a fluoropyrimidine, with or without immunotherapy (treatment that helps the immune system fight cancer).
Have tumor tissue that is HER2 negative, meaning the tumor does not show too much of the HER2 protein, based on approved testing rules.
Be able to provide a core biopsy or excisional biopsy, meaning a sample taken from a tumor, from a tumor area that has not been treated with radiation, and the sample must be taken after the most recent cancer treatment.
Have side effects from previous cancer treatments that are Grade 1 or better, meaning mild or back to the person’s usual level, except for hair loss and vitiligo (loss of skin color in patches). Endocrine-related side effects, meaning problems with hormone-producing glands, are allowed if they are well controlled with hormone replacement.
Have an ECOG performance status of 0 or 1, meaning the person is fully active or only slightly limited in daily activities.
Have an expected life span of at least 3 months.
If there is a history of hepatitis B, have received antiviral treatment for at least 4 weeks and have an undetectable viral load, meaning the virus is not found in the blood before joining the study.
If there is a history of hepatitis C, have an undetectable viral load at screening, meaning the virus is not found in the blood when first checked for the study.
If living with HIV, have the infection well controlled with ART (antiretroviral therapy, medicine that lowers the HIV amount in the body).

Who Cannot Join the Study?

The cancer must not be a squamous cell or undifferentiated gastroesophageal cancer.
Blood pressure must not be uncontrolled, meaning it is at or above 150/90 mm Hg.
There must not be fluid buildup around the lungs, in the abdomen, or around the heart that needed drainage or water pills within the past 2 weeks.
The patient must not have had major surgery within the past 28 days, a central venous access device placed within the past 7 days, or planned major surgery after starting study treatment. A central venous access device is a tube placed into a large vein to give medicines or fluids.
The patient must not be receiving therapeutic anticoagulation such as warfarin, low-molecular-weight heparin, or similar blood-thinning medicines used to prevent clots.
The patient must not be taking long-term nonsteroidal anti-inflammatory drugs or other antiplatelet medicines. These are medicines that can increase bleeding risk.
The patient must not have had deep vein thrombosis, pulmonary embolism, or another major blood clot problem within the past 3 months. Deep vein thrombosis is a clot in a deep vein, usually in the leg. Pulmonary embolism is a clot in the lung.
The patient must not have important bleeding disorders, vasculitis (inflammation of blood vessels), or a significant bleeding episode from the digestive tract within the past 3 months.
The patient must not have a history of gastrointestinal perforation or fistula within the past 6 months. A perforation is a hole in the digestive tract. A fistula is an abnormal connection between body parts.
A person with HIV must not have a history of Kaposi’s sarcoma or Multicentric Castleman’s Disease.
The patient must not have previously received a treatment that targets TROP2 or HER3, a topoisomerase 1 inhibitor-based ADC, a topoisomerase 1 inhibitor-based chemotherapy, or any past systemic treatment that targets the VEGF or VEGFR pathways. An ADC is an antibody-drug conjugate, a type of medicine that carries a drug to cancer cells.
The patient must not have lost more than 20% of body weight in the 3 months before the first study dose.
The patient must not have received other systemic anticancer therapy within 4 weeks before the first study dose. Systemic treatment is treatment that travels through the whole body.
The patient must not have received radiotherapy within 2 weeks before starting study treatment, and must not have radiation side effects that need corticosteroids. Radiotherapy is treatment with radiation.
The patient must not have received a live vaccine or live-attenuated vaccine within 30 days before the first study dose. Killed vaccines are allowed.
The patient must not have received another investigational agent or used an investigational device within 4 weeks before study treatment. Investigational means not yet approved for general use.
The patient must not have another cancer that is growing or has needed active treatment within the past 3 years, except for certain skin cancers and some early cancers that were completely treated.
The patient must not have active central nervous system metastases or carcinomatous meningitis. Central nervous system metastases are cancer spread to the brain or spinal cord. Carcinomatous meningitis is cancer involving the lining around the brain and spinal cord.
The patient must not have an active infection that needs treatment through the whole body.
The patient must not have active hepatitis B or hepatitis C infection. These are viral infections of the liver.
The patient must not have pneumonitis or interstitial lung disease, and it must not be unclear on screening scans whether these lung problems are present. Pneumonitis is inflammation of the lungs, and interstitial lung disease is scarring or inflammation in the lung tissue.
The patient must not have a severe allergy reaction, called grade 3 or higher hypersensitivity, to MK-2870, HER3-DXd, any of their ingredients, or another biologic therapy. Biologic therapy is treatment made from living sources or living cells.
The patient must not have had documented severe dry eye syndrome, severe Meibomian gland disease, blepharitis, or severe corneal disease that could slow healing of the cornea. The cornea is the clear front part of the eye.
The patient must not have fully recovered from major surgery or have ongoing problems from surgery.
The patient must not have grade 2 or higher peripheral neuropathy. Peripheral neuropathy means nerve damage that can cause numbness, tingling, or pain in the hands or feet.
The patient must not have active inflammatory bowel disease that needs medicines that suppress the immune system, and must not have a past history of inflammatory bowel disease. Inflammatory bowel disease includes long-term inflammation of the intestines.
The patient must not have a serious or nonhealing wound, a peptic ulcer, or a bone fracture within 28 days before allocation/randomization. A peptic ulcer is a sore in the stomach or upper intestine.
The patient must not have a bowel obstruction, a history of inflammatory enteropathy, or extensive removal of the intestine with chronic diarrhea. Bowel obstruction means a blockage in the intestine, and inflammatory enteropathy means inflammation of the intestines.
The patient must not have uncontrolled, significant heart disease or blood vessel disease, or significant cerebrovascular disease, which means disease of the blood vessels in the brain.
The patient must not have had a major arterial blood clot event within 6 months, including heart attack, unstable angina (new or worsening chest pain), stroke, or transient ischemic attack (a temporary stroke-like episode).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Technische Universitaet Dresden	Dresden	Germany
Oslo Universitetssykehus HF	Oslo	Norway
Haematologisch Onkologische Praxis Eppendorf	Hamburg	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
Centre Hospitalier Universitaire De Lille	Lille	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France

Other Sites

Site Name	City	Country
Krankenhaus Nordwest GmbH	Frankfurt	Germany
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)	Munich	Germany
Ospedale San Raffaele S.r.l.	Milan	Italy
Universita’ Di Pisa	Pisa	Italy
Hopital Beaujon	Clichy	France
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Ivrewcpp Rmtdrtsrx Pnd Lv Slfhep Drd Telqbw Dweo Ajsfwiq Ieki Sdcxpz	Meldola	Italy
Uoakajgtgihrfdhlcphgi Dwfyvfdnssl Ayi	Duesseldorf	Germany

Trial status

Country	Status	Recruitment Start
France	Recruiting	01.07.2024
Germany	Recruiting	01.07.2024
Italy	Recruiting	01.07.2024
Norway	Recruiting	01.07.2024

Trial locations

Investigated drugs:

Paclitaxel is a chemotherapy medicine given through a vein. In this trial, it is part of the standard treatment used to help slow or stop the growth of cancer cells.

MK-2870 is an investigational cancer medicine. It is being tested to see whether it can safely and effectively treat advanced stomach or gastroesophageal cancer, especially when combined with standard treatment.

Patritumab deruxtecan is another investigational cancer medicine given through a vein. It is designed to target cancer cells more directly and is being studied to see how well it works and how safe it is in this cancer setting.

Ramucirumab is a cancer treatment given through a vein. It works by blocking signals that help tumors grow new blood vessels, which may help slow the cancer’s growth.

Paracetamol is a pain-relief medicine taken by mouth. In this trial, it is used as supportive care to help reduce pain or discomfort related to treatment.

Glucocorticoids are steroid medicines used as supportive care. They may help lower inflammation and reduce side effects from cancer treatment, such as allergic-type reactions or nausea.

H2-receptor antagonists are medicines given through a vein that help reduce stomach acid. They are used as supportive care to help prevent stomach irritation and some treatment-related reactions.

Antihistamines for systemic use are medicines used to help prevent allergic-type reactions. In this study, they are part of supportive care given to make treatment safer and easier to tolerate.

Gastroesophageal cancer – Gastroesophageal cancer is a cancer that starts in the area where the esophagus meets the stomach. It usually grows by invading nearby tissue and can spread to lymph nodes and other parts of the body. As it progresses, it may cause narrowing of the passage for food and affect normal swallowing and digestion.

Trial ID:

2023-509306-29-00

Protocol code:

MK-3475-06D

Trial Phase:

Human Pharmacology (Phase I) – Other

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Evaluation of Safety and Efficacy of MK-2870 and Paclitaxel in Second-Line Treatment of Advanced/Metastatic Gastroesophageal Adenocarcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?