A First-in-Human, Phase 1 Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of a Single-Induction Dose of convertibleCARTM-T Cells Armed With MicAbodyTM Protein (ASP2802) Followed by Maintenance Booster Doses of the MicAbody Protein in Patients With CD20-Positive Relapsed or Refractory B-Cell Lymphomas

CAR-T cell therapy is a type of treatment for people with certain lymphomas. T-cells are white blood cells that help to fight infections. CAR-T cell therapy improves the body's T-cells to help them better fight cancer cells.

ASP2802 is a type of CAR-T cell therapy given with MA-20. MA-20 is a protein that helps the CAR-T cell therapy work inside the body.

Before ASP2802 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help find a suitable dose for future studies and check for potential medical problems from the treatment.

In this study, ASP2802 is being tested in humans for the first time. ASP2802 has already been tested in the laboratory and in animals. This is the standard way new potential treatments are developed.

People taking part in this study will be adults with CD20-positive B-cell lymphomas. CD20 is a protein found on a type of white blood cell called a B-cell. Some people with B-cell lymphomas have more CD20 on these cells. Their cancer will have come back after it had disappeared with earlier therapy (relapsed) or it will have become resistant to previous treatment (refractory).

The main aims of the study are to check the safety of ASP2802, how well it is tolerated, and to find a suitable dose of ASP2802.

This is an open-label, adaptive study. Open-label means that people in this study and clinic staff will know that people will receive ASP2802 treatment. Adaptive means the treatments may change, depending on earlier results in the study.

There will be 3 groups of people in this study and 3 doses of ASP2802. Groups A, B and C will receive ASP2802 treatment. Group A will start treatment first with a low dose of ASP2802. If Group A tolerates the low dose of ASP2802, then Group B will receive the higher dose of ASP2802. If Group B tolerates the higher dose of ASP2802, then Group C will receive the highest dose of ASP2802.

There are several steps in this treatment. First, T-cells are removed from the blood by inserting a small tube (cannula) into a vein and connecting it to a machine that separates out the blood cells. The machine collects the T-cells and returns the rest of the blood cells back into the bloodstream. The collected T-cells are sent to the lab to be changed into improved T-cells (with ASP2802) to fight the cancer. This may take several weeks, so people in the study may receive extra treatment, to keep the cancer under control during this time.

Before the improved T-cells go back in the body, people will visit the clinic so that the study doctors can do a series of checks to make sure they are well enough to receive the T-cells. A few days before the improved T-cells go back into the body, people in the study will have chemotherapy for 3 days. This is to make sure the cancer is at its lowest level before people are treated with ASP2802. Then, the improved T-cells are fed back into the bloodstream using a drip attached to the cannula. After this, a booster of MA-20 will be given at the set dose by infusion on Day 3 and Day 17 in a 28-day cycle. If people respond well to treatment, they may stay on the same dose during the next cycle; if they have medical problems from the treatment, they may get a lower dose during the next cycle. The next group of people may receive a different dose (higher or lower) of MA-20 depending on the results from the previous group. People in the study will continue receiving MA-20 in this way until: they have certain medical problems from the treatment on the lowest dose of MA-20; they start other cancer treatment; their cancer gets worse; they or the study doctor decides they should stop treatment; they do not come back for treatment.

After treatment has finished, people in the study will visit the clinic regularly for 2 years and continue to be monitored for up to 15 years.

Some people may be treated again with MA-20. This may happen for people who have responded to treatment and then relapse within a year, or for people that have a partial response and have a slow growing lymphoma.

During the study, people will visit the study hospital many times. During most visits, the study doctors will do a medical examination, blood tests and check vital signs. Vital signs include temperature, breathing rate, blood pressure, blood oxygen levels, and heart rate. They will also check for medical problems. In some visits, computerized tomography (CT) scans and electrocardiograms (ECGs) to check the heart rhythm will also be done.

People will have several hospital stays during their treatment. This may be during their chemotherapy, then from Days -1 to 7 and Days 17 to 21 during the cycle 1 of MA-20. Day -1 means 1 day before treatment with ASP2802. During this time, people will be closely monitored for medical problems, have EGCs and have a biopsy taken. During the extra cycles of MA-20, there will be the option of staying overnight.