Azienda Ospedaliera Universitaria Senese
Responsive
Siena, Italy
Recruiting
Study of Nivolumab, Ipilimumab, and ASTX727 for Melanoma and Lung Cancer Patients Resistant to Anti-PD-1/PD-L1 Therapy
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What is this trial about?
A plain-language summary of the goals, design and what participants do
This clinical trial is focused on studying treatments for patients with two types of cancer: melanoma and non-small cell lung cancer (NSCLC). These patients have shown resistance to a type of therapy known as anti-PD-1/PD-L1. The study will explore the effectiveness of combining two medications, nivolumab and ipilimumab, with an oral medication called ASTX727, which contains the active substances decitabine and cedazuridine. Alternatively, some patients will receive only the combination of nivolumab and ipilimumab. Nivolumab and ipilimumab are types of medications known as monoclonal antibodies, which help the immune system fight cancer cells. Decitabine and cedazuridine work together to inhibit certain enzymes that can affect cancer cell growth.
The purpose of this study is to assess how well these treatment combinations work in patients who have not responded to previous therapies. Participants will receive the treatments over a period of up to 24 months. The study will involve regular assessments to monitor the response of the cancer to the treatment, as well as evaluations of the safety and any side effects experienced by the participants. These assessments will be conducted using imaging techniques like MRI or CT scans to measure changes in the size of the tumors.
Throughout the study, participants will be closely monitored by healthcare professionals to ensure their safety and to gather data on the effectiveness of the treatments. The study aims to provide valuable information that could lead to improved treatment options for patients with melanoma and NSCLC who have limited responses to existing therapies. The trial is expected to continue until the end of 2028, allowing researchers to collect comprehensive data on the long-term effects and benefits of the treatment combinations.
The research process
The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.
Who can join the trial?
10 criteria
- Must be willing and able to give written informed consent, which means agreeing to participate after understanding the study details.
- Women who can have children must not be pregnant or breastfeeding and must have a negative pregnancy test before starting the study. They must use effective birth control methods during the study and for 6 months after the last dose of the study drug.
- Men must use two reliable birth control methods while on the study drugs and for 7 months after the last dose. This is to prevent fathering a child during this time.
- Participants must be 18 years or older.
- For the melanoma group, participants must have a confirmed diagnosis of malignant melanoma that cannot be surgically removed and have shown resistance to certain therapies. They must have measurable lesions that can be biopsied.
- For the NSCLC group, participants must have a confirmed diagnosis of non-small cell lung cancer without specific genetic mutations. They must have Stage IV cancer with resistance to certain therapies and measurable lesions that can be biopsied.
- Participants must have had at least 4 weeks since their last treatment and must have recovered from any side effects of previous treatments.
- Must have a life expectancy of more than 16 weeks.
- Must have adequate organ function, which includes specific levels of white blood cells, platelets, hemoglobin, and kidney and liver function.
- Must test negative for HIV, Hepatitis B, and Hepatitis C. If tests are positive but not indicative of an active or chronic infection, participation may still be possible after discussion with the study team.
Who cannot join the trial?
4 criteria
- Patients who have not shown resistance to **anti-PD-1/PD-L1 therapy**. This means the treatment that blocks certain proteins to help the immune system fight cancer has not stopped working for them.
- Patients who are not diagnosed with **MM** (Multiple Myeloma) or **NSCLC** (Non-Small Cell Lung Cancer).
- Patients who are not within the specified age range for the study.
- Patients who are not able to give informed consent or are part of a vulnerable population that cannot participate in the study.
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Investigated drugs
Nivolumab
is a medication used in this trial to help the immune system attack cancer cells. It is a type of immunotherapy known as a checkpoint inhibitor, which works by blocking a protein that prevents the immune system from attacking cancer cells effectively.
Ipilimumab
is another immunotherapy drug used in combination with nivolumab in this trial. It also helps the immune system to recognize and destroy cancer cells by targeting a different protein that can slow down the immune response against cancer.
Decitabine/Cedazuridine (ASTX727)
is an oral medication used in this trial to enhance the effects of the immune system on cancer cells. It is a combination of two drugs that work together to modify the DNA of cancer cells, making them more susceptible to being attacked by the immune system.
What is already known about the treatment
Nivolumab
Nivolumab is administered as an intravenous infusion. It is currently used in clinical settings and extensively documented in medical literature for its role in cancer immunotherapy. The main therapeutic indications include treatment of melanoma and non-small cell lung cancer (NSCLC), particularly in patients resistant to anti-PD-1/PD-L1 therapy. At the molecular level, nivolumab works by blocking the PD-1 protein on T cells, enhancing the immune system's ability to attack cancer cells. It is classified as an immune checkpoint inhibitor.
Ipilimumab
Ipilimumab is given through intravenous infusion. It is well-established in medical practice and literature as a treatment for certain types of cancer. It is primarily indicated for melanoma and NSCLC, especially in cases resistant to anti-PD-1/PD-L1 therapy. Ipilimumab functions by inhibiting the CTLA-4 protein on T cells, which boosts the immune response against cancer cells. It belongs to the class of immune checkpoint inhibitors.
Decitabine/Cedazuridine (ASTX727)
This medication is administered orally. It is currently being explored in clinical trials and is documented in medical literature for its potential in cancer treatment. The main therapeutic indication is for use in combination with other drugs for melanoma and NSCLC resistant to anti-PD-1/PD-L1 therapy. At the molecular level, decitabine acts as a DNA methyltransferase inhibitor, which can reactivate tumor suppressor genes, while cedazuridine enhances its bioavailability. It is classified as a hypomethylating agent.
Investigated diseases
Malignant Melanoma
Malignant melanoma is a type of skin cancer that originates in the pigment-producing melanocytes. It often appears as a new or changing mole on the skin, which may be asymmetrical, have irregular borders, or vary in color. As it progresses, it can invade deeper layers of the skin and potentially spread to other parts of the body, including lymph nodes and internal organs. Early stages may be confined to the skin, but advanced stages involve metastasis. The progression can vary significantly between individuals, with some experiencing rapid changes and others having a more indolent course. Regular skin checks and monitoring of moles are important for early detection.
Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of cases. It typically begins in the epithelial cells lining the lungs and can grow into a large mass, potentially invading nearby tissues. As it advances, NSCLC can spread to lymph nodes and distant organs such as the brain, liver, and bones. Symptoms may include a persistent cough, chest pain, and difficulty breathing. The disease is often diagnosed at an advanced stage due to the subtlety of early symptoms. The progression of NSCLC can vary, with some tumors growing slowly and others more aggressively.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2024-518891-29-00Protocol codeNIBIT-ML-1Estimated enrolment148 patientsSponsorFondazione NIBIT Onlus
sourced from the EU Clinical Trials Register and site verification
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