Randomizowane, prowadzone metodą otwartej próby, wieloośrodkowe badanie III fazy oceniające skuteczność i bezpieczeństwo glofitamabu w skojarzeniu z gemcytabiną i oksaliplatyną w porównaniu z rytuksymabem w skojarzeniu z gemcytabiną i oksaliplatyną u pacjentów z nawracającym/ opornym chłoniakiem rozlanym z dużych komórek B.

1. Why is this study needed?

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. It affects a type of immune cell called B cells. It often starts in lymphoid tissues and can spread to other organs. The cells look bigger than other cancers when seen under a microscope.

Rituximab given with 2 chemotherapy medicines – gemcitabine (Gem) and oxaliplatin (Ox), often called ‘GemOx’ – is widely used when initial treatments do not work. However it is not approved by health authorities (like the U.S. Food and Drug Administration and European Medicines Agency). New treatments are needed for people with DLBCL that does not respond to or worsens after the first or second treatment.

This study is testing a medicine called glofitamab combined with GemOx. It is being developed to treat DLBCL. Glofitamab plus GemOx is an experimental combination of medicines. This means health authorities have not approved this combination for the treatment of DLBCL after previous treatment has not worked.

This study aims to compare the effects of glofitamab plus GemOx versus rituximab plus GemOx in people with DLBCL that has come back or worsened after previous treatment.

2. Who can take part in the study?

People of 18 years of age or older with DLBCL can take part in the study if they have had at least 1 previous treatment that did not work and cannot be given high-dose chemotherapy followed by a stem-cell transplant.

People may not be able to take part in this study if they have DLBCL that has certain changes (gene mutations) or is fast-growing, or if they have been treated with rituximab plus GemOx, GemOx, glofitamab or similar medicines before. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 1 month before the start of treatment.

Treatment will be given in ‘cycles’. A treatment cycle is the period of treatment and recovery time before the next set of treatment is given. In this study, each cycle will last 3 weeks.

Everyone who joins this study will be placed into 1 of 2 groups randomly (like flipping a coin) and given either:

• Glofitamab plus GemOx given as a drip into the vein for up to 8 cycles, then glofitamab alone for 4 cycles
• Rituximab plus GemOx given as a drip into the vein for up to 8 cycles

Participants will have a 2 in 3 chance of being placed in the glofitamab group and a 1 in 3 chance of being placed in the rituximab group. This means that more people will be in the glofitamab group than the rituximab group.

Participants in the glofitamab group will be required to stay in the hospital overnight the first time they are given study treatment. They will be given another medicine called ‘obinutuzimab’ as a drip into the vein before they are given glofitamab for the first time. This is a safety measure to reduce the chance of an unwanted effect called ‘cytokine release syndrome’ – when the immune system reacts in an unusual way to an infection or cancer immunotherapy. This can cause a variety of symptoms, such as a fever, nausea, headache, and rash. If this unwanted effect happens, another medicine called ‘tocilizumab’ will be given as a drip into the vein.

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants every 1 to 3 weeks. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have 1 follow-up visit 6 weeks after their last dose of study treatment during which the study doctor will check on the participant’s wellbeing. The study doctor will continue to check the participants’ wellbeing through their medical records, follow-up telephone calls or hospital visits every 3 months, for as long as the participant agrees to it. Total time of participation in the study could be up to 5 years depending on how well treatment works. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main results measured in the study to assess if the medicine has worked is how long participants live.

Other key results measured in the study include:

• How long participants live without their cancer getting worse
• The number of participants who do not have cancer on tests or scans after treatment, and how long this response lasts
• How many participants have a reduction of their cancer after treatment, and how long this response lasts
• The time it takes for a participant to have a significant worsening in their lymphoma symptoms, physical health or level of tiredness
• The number and seriousness of unwanted effects

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with glofitamab, rituximab, gemcitabine, oxaliplatin, obinutuzimab and tocilizumab

Participants may have unwanted effects of the drugs used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Participants will be told about the known unwanted effects and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include:

• Glofitamab – cytokine release syndrome, fever, and a low level of white blood cells
• Rituximab – infections, itching and rash
• Gemcitabine and oxaliplatin – wanting to throw up, a low level of white blood cells and damage to the nerves outside the brain and spinal cord
• Obinutuzimab – a reaction to the drip into a vein, infections, fever
• Tocilizumab – an infection that makes a person have a sore throat, cough, runny nose and sneezing

Known unwanted effects of a drip into the vein include throwing up, wanting to throw up, a feeling of coldness that makes the body shiver, fever, pain or discomfort in the head, shortness of breath, and cough. The study medicines may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.

For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04408638

Trial-identifier: NCT04408638