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Low-dose nivolumab in patients with advanced cancer and high tumor mutational burden (TMB‑high)

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on patients with advanced neoplasms that are classified as TMB-high, meaning the tumors contain a large number of genetic changes. The investigational treatment is a low dose of the intravenous medicine nivolumab, which belongs to a class of therapies that help the body’s immune system recognize and attack cancer cells.

The purpose of the study is to evaluate whether this low‑dose approach can produce a beneficial tumor response, measured by the overall response rate (ORR). Participants will receive the infusion at scheduled intervals over several months and will have regular check‑ups to monitor safety and any changes in the tumors. The study will follow each participant from the first dose through the observation period to collect the required information.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Baseline assessment
You will undergo a series of initial tests to record your current health status. this includes a review of your medical history, a physical examination, blood tests, and imaging studies such as scans of the tumor area. these results create a reference point for later comparisons.
The purpose of the baseline assessment is to confirm eligibility for the study and to document the characteristics of the tmb-high advanced neoplasm before any treatment is given.
Step 2
First infusion of nivolumab
You will receive the study medication, nivolumab, as an intravenous infusion. the concentration is 10 mg per milliliter, and the prescribed dose is 10 mg per infusion.
The infusion is administered through a vein, typically in a clinical setting, and takes a short period of time while medical staff monitor you for any immediate reactions.
Step 3
Scheduled infusion visits
After the first dose, you will return for additional infusions of nivolumab according to the study schedule. each infusion will be the same 10 mg dose given by intravenous infusion.
The exact timing of each visit (for example, every two to four weeks) is defined by the trial protocol and will be communicated to you by the study team.
Step 4
Monitoring visits
At each infusion visit, you will also have routine monitoring. this includes checking vital signs, a brief physical exam, and blood tests to assess organ function and detect any side effects.
The staff will ask you about any new symptoms you may have experienced since the previous visit.
Step 5
Imaging assessments
Periodically, you will undergo imaging studies such as CT or MRI scans. these scans evaluate how the tumor is responding to the treatment and are used to calculate the overall response rate, the primary goal of the study.
The schedule for imaging (for example, every eight weeks) follows the trial protocol.
Step 6
End‑of‑treatment evaluation
When the planned treatment period ends, you will have a final set of assessments. this includes a physical exam, blood tests, and imaging to determine the overall effect of the therapy.
The results will be compared with the baseline data to assess the study’s primary endpoint.
Step 7
Follow‑up period
After the treatment phase, you will continue to be monitored for a defined follow‑up period. during this time, periodic visits may include additional blood tests or imaging to ensure long‑term safety and to observe any delayed effects of the medication.
The duration and frequency of follow‑up visits are outlined in the study protocol.

Who can join the trial?

9 criteria

You must sign an informed consent form before any study procedures begin, meaning you agree after understanding what the study involves.
You must be at least 18 years old when you sign the consent.
You must have a solid tumor that a doctor has confirmed by looking at it under a microscope (histologically confirmed), the tumor must be classified as TMB‑high (it has many genetic changes), and you must have tried and not benefited from all standard treatments that could cure or extend life.
Your overall health level, measured by the ECOG performance status, must be 0 or 1 (you are fully active or have some symptoms but can still carry out most daily activities).
Your recent lab tests (within the last 14 days) must show that your blood, kidneys, and liver are working well:
- Blood: an absolute neutrophil count of at least 1500 per microliter, a platelet count of at least 100,000 per microliter, and a hemoglobin level of at least 9 g/dL without needing blood‑boosting medicines or transfusions.
- Kidneys: a serum creatinine level not more than 1.5 times the normal upper limit, or a 24‑hour creatinine clearance of at least 60 mL per minute if creatinine is higher.
- Liver: a bilirubin level not more than 1.5 times the normal upper limit (or a direct bilirubin that is normal if total bilirubin is high), and liver enzymes AST and ALT not more than 2.5 times the normal upper limit (or not more than 5 times if cancer has spread to the liver).
- If you are a woman who could become pregnant, you must have a negative urine or blood pregnancy test taken within the last 72 hours; if the urine test is positive or unclear, a blood test will be required.
- You must provide a sample of your tumor tissue (either an old sample or a new biopsy) so the study can confirm the TMB‑high status.

Who cannot join the trial?

13 criteria

You cannot already be receiving a reimbursed immune checkpoint inhibitor (ICI) treatment, which is a type of cancer medicine that helps the immune system attack tumors.
You cannot take part in any other experimental procedures while you are in this study.
You cannot have a significantly weakened immune system. This includes a diagnosed immune deficiency, an opportunistic infection (an infection that occurs because the immune system is weak), or taking strong immune‑suppressing medicines for more than two weeks, or high‑dose steroids (more than 10 mg per day of prednisone or equivalent) within seven days before the first study dose.
You cannot have a known infection with human immunodeficiency virus (HIV), which is the virus that can lead to AIDS.
You cannot have a known active infection with hepatitis B or hepatitis C, which are viral infections that affect the liver.
You cannot have active cancer spread to the brain or spinal cord, called central nervous system (CNS) metastases. Even if brain tumors were treated before, they must be stable and you must not be using high‑dose steroids (more than 8 mg per day of methylprednisone).
You cannot have a history of immune deficiency such as inherited immune disorders, organ transplant, or leukemia (a cancer of the blood‑forming cells).
You cannot have a recent or active autoimmune disease that caused symptoms in the lungs, kidneys, blood vessels, or other organs, unless it was a mild condition like vitiligo or resolved childhood asthma. Autoimmune disease means the body mistakenly attacks its own tissues.
You cannot have had another cancer in the past five years, except for certain low‑risk cancers that are fully treated and show no disease: non‑melanoma skin cancer, cervical carcinoma in situ, breast ductal carcinoma in situ, certain prostate conditions, or superficial bladder cancer.
You cannot have been treated before with an immune checkpoint inhibitor.
You cannot have received chemotherapy, radiation therapy, targeted therapy, biological cancer therapy, or major surgery within 28 days before joining the study, and you must have fully recovered (no more than mild side effects, described as CTCAE grade 1) from any previous cancer treatment.
You cannot be currently enrolled in another experimental drug or device study, or have finished another such study less than 28 days ago.
You cannot be expected to need another cancer treatment during the study, except for local radiation used only to relieve bone pain.

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Verified sites

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Vrije Universiteit Brussel
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Jette, Belgium

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Investigated drugs

OPDIVO is a medicine that contains the active ingredient nivolumab. It is an immunotherapy drug that helps the body’s immune system notice and fight cancer cells. In this study, patients with advanced cancers that have a high number of genetic mutations (called TMB‑high) receive OPDIVO through an IV infusion at a low dose. The researchers are testing whether this low dose can still work well to treat the cancer.

Nivolumab

What is already known about the treatment

Nivolumab - Nivolumab is given as a solution for infusion that is injected into a vein. It is an approved cancer medicine and has been extensively studied in clinical research. It is used mainly for treating advanced cancers, especially those that have a high tumor mutation burden. It works by blocking the PD‑1 protein on immune cells, helping the body’s immune system attack cancer, and it belongs to the class of immune checkpoint inhibitors.

Investigated diseases

TMB-high advanced neoplasms - These are cancers that contain a large number of genetic mutations and are in an advanced stage, meaning they have spread beyond the original location or cannot be removed surgically. They often grow and spread more rapidly than tumors with lower mutation counts. The high mutational load makes the tumor cells appear more distinct to the immune system. Over time the disease can involve multiple organs or lymph node groups.