A clinical trial to look at how safe glofitamab with gemcitabine and oxaliplatin (GlofitGemOx) is and how well it works in people living in the U.S. with fast-growing B-cell non-Hodgkin’s lymphoma that has come back or did not respond to previous treatment, how the body processes it, and the effects it has

1. Why is the GO44900 clinical trial needed?

B-cell non-Hodgkin lymphoma is a blood cancer that affects a type of immune cells called B cells. Diffuse large B-cell lymphoma (DLBCL) is the most common type of fast-growing lymphoma (aggressive B-cell nonHodgkin’s lymphoma). It often starts in tissue that contains white blood cells and can spread to other organs. Standard treatment for DLBCL is a combination of chemotherapy and immunotherapy. For some people, their cancer does not respond to standard treatments or therapies (their disease is refractory) or their cancer returns (relapses). This is called relapsed or refractory (R/R) DLBCL. New drug combinations are needed to treat R/R DLBCL.

Glofitamab is an immunotherapy drug approved by health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) for the treatment of R/R DLBCL on its own, when given after at least 2 therapies. However, glofitamab with chemotherapy drugs gemcitabine and oxaliplatin (Glofit-GemOx) is a treatment combination that has not been approved in the U.S. for treating aggressive B-cell non-Hodgkin’s lymphoma. This clinical trial aims to test the safety of Glofit-GemOx in people living in the U.S. with R/R aggressive B-cell non-Hodgkin’s lymphoma, how well the treatment combination works, how the body processes Glofit-GemOx, and how the treatment works in the body and the effects it has.

2. How does the GO44900 clinical trial work?

This clinical trial is recruiting people in the U.S. with R/R aggressive B-cell non-Hodgkin’s lymphoma, with a focus on enrolling Hispanic, Latino, Black or African American participants. People who take part in this clinical trial (participants) will be given the Glofit-GemOx treatment combination for up to 6 months, followed by glofitamab alone for up to 3 months. In total, treatment will last for up to 9 months, or until their cancer gets worse. Participants will be required to stay overnight in the hospital the first time they are given glofitamab for safety monitoring. During the trial, treatment will be given in 3-week cycles. A treatment cycle is made up of the days that treatment is given, plus the recovery time.

The clinical trial doctor will see the participants 4 times during Cycle 1, then 1 to 2 times during each cycle up to Cycle 12 (Cycles 2 to 12). Following the last dose of treatment, the clinical trial doctor will see the participants once after 6 to 8 weeks. Thereafter, participants will receive a follow-up telephone call from the study doctor every 3 months to check on their well-being for as long as they agree to it. Total time of participation in the clinical trial will be about 5 years. Participants can stop trial treatment and leave the clinical trial at any time without penalty or loss of benefits to which the participant is otherwise entitled.

3. What are the main endpoints of the GO44900 clinical trial?

The main clinical trial endpoints (the main results measured in the trial to see if the drug has worked) are:

• The number, type and seriousness of unwanted effects (safety and tolerability)
• The number of participants who stop treatment due to unwanted effects
• The number of participants who have no signs of disease remaining after treatment on their scans

The other clinical trial endpoints include:

• The number of participants who have a specific level of reduction in the size of their tumour on scans and how much time this lasts if the cancer worsens
• The amount of time between the start of treatment and the participants’ cancer getting worse
• How long participants live

4. Who can take part in this clinical trial?

People can take part in this trial if they are aged 18 years or older and have received at least 1 treatment for their aggressive B-cell non-Hodgkin’s lymphoma, and are living in the U.S. People may not be able to take part in this trial if they:

• Have certain cancers other than aggressive B-cell non-Hodgkin’s lymphoma
• Have had glofitamab, gemcitabine or oxaliplatin treatment before
• Have had certain treatments such as an organ transplant, or are eligible for a stem cell transplant
• Have certain medical conditions such as stroke, heart disease, lung disease, autoimmune disease and liver disease or an active infection
• Are pregnant or breastfeeding or are planning to become pregnant. This applies until 1 and a half years after the trial

5. What treatment will participants be given in this clinical trial?

Everyone who joins this clinical trial will be given treatment in 12 cycles each lasting 3 weeks. To reduce the chance of unwanted effects from glofitamab treatment, participants will be given increasingly higher doses (called ‘step-up’ doses). Participants will be given:

• Glofit-GemOx as a drip into the vein once every 3 weeks (Cycles 1 to 8), with glofitamab given in 2 increasing doses on Day 8 and 15 of Cycle 1
• Glofitamab as a drip into the vein once every 3 weeks (Cycles 9 to 12)

Everyone will also be given a pre-treatment drug called ‘obinutuzumab’ as a drip into the vein, 1 week before they are given glofitamab. This is to reduce the risk of an unwanted effect called ‘cytokine release syndrome,’ which happens when the immune system reacts in an unusual way to cancer immunotherapy, causing a variety of symptoms, such as a fever, wanting to throw up (nausea), headache, and rash. If a participant experiences cytokine release syndrome they may receive another medicine called tocilizumab as a drip into the vein.

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

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).

Risks associated with the clinical trial drugs
Participants may have unwanted effects from the drugs used in this clinical trial. Unwanted effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly.

Participants will be told about the known unwanted effects of Glofit-GemOx, obinutuzumab and tocilizumab, and possible unwanted effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known unwanted effects of drips into the vein.

Potential benefits associated with the clinical trial
Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.