An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

1. Why is the NP39488 clinical trial needed?

B-cell non-Hodgkin lymphoma (NHL) is a common type of cancer that affects a type of immune cell called B-cells. Although there has been progress in treating NHL, many people who have NHL may not respond to treatment (their disease is refractory) or their cancer returns (relapses). New treatment combinations, such as glofitamab with atezolizumab or polatuzumab vedotin, could help people with relapsed or refractory (R/R) B-cell NHL to live longer. Glofitamab is approved by health authorities for the treatment of a type of B-cell NHL (known as 'diffuse large B-cell lymphoma'). Glofitamab and atezolizumab are the experimental drugs in this clinical trial, which means health authorities have not approved glofitamab on its own for treating other types of B-cell NHL. Polatuzumab vedotin is only approved by the health authorities in some countries for treating B-cell NHL so polatuzumab vedotin may not be available to all participants who take part in the trial. 

This clinical trial aims to test the safety and effectiveness of different dose combinations of glofitamab with atezolizumab or polatuzumab vedotin in people with R/R B-cell NHL and to understand how the body processes these treatment combinations.

2. How does the NP39488 clinical trial work?

This clinical trial is recruiting people with R/R B-cell NHL. People who take part in this clinical trial (participants) will be given the clinical trial treatment glofitamab in combination with atezolizumab for up to 1 year OR glofitamab in combination with polatuzumab vedotin for up to 9 months unless they have very severe side effects, their cancer gets worse or they decide to leave the trial. Treatment will be given in 21-day cycles – a treatment cycle includes receiving the treatment and the recovery time before the next dose is given. Participants receiving glofitamab in combination with atezolizumab who have no cancer on scans after 8 cycles of treatment (about 6 months), will stop receiving the clinical trial treatment and will continue to be monitored in the trial – if a participant’s cancer returns then another 9 cycles of treatment will be provided. 

The clinical trial doctor will see them 5 times during the first 2 weeks, and then every 3 weeks. These hospital visits will include checks to see how the participant responds to the treatment and any side effects they may have. Participants will be seen 1 month after the last dose of treatment, then every 3–6 months for as long as they agree to it. Total time of participation in the clinical trial could be more than 3 years. Participants can stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the NP39488 clinical trial?

The main clinical trial endpoint (the main result measured in the trial to see if the drug has worked) is the maximum dose of glofitamab that can be given with other anti-cancer treatments before very severe side effects occur. The other clinical trial endpoints include:

• The number and seriousness of any side effects
• How the body processes the anti-cancer drugs and how the drugs affect the immune system
• The number of participants whose cancer disappears or gets smaller and the amount of time this lasts if disease then progresses
• The number of participants whose cancer disappears, gets smaller or stays the same
• The amount of time it takes for participants to first have a response to treatment and for the cancer to disappear 
• The amount of time between the start of the trial and participants’ cancer worsening 
• 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 over and have no other treatment options available for their NHL. People may not be able to take part in this trial if they have certain lymphomas, have/had certain medical conditions such as infections, stroke, heart disease, autoimmune disease or other advanced cancers, or have received certain other treatments including organ or stem-cell transplant. People who are pregnant or breastfeeding or are planning to become pregnant during or soon after the clinical trial also cannot take part.

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

Everyone who joins this clinical trial will be placed into a group depending on the treatments available in their country and the clinical trial doctors' decision, and given either:

• Glofitamab and atezolizumab 
  • glofitamab as an infusion into the vein on Days 1 and 8 for the first 21-day cycle, and then every 3 weeks from Cycle 2 for up to 17 cycles
  • atezolizumab as an infusion into the vein every 3 weeks from Cycle 2 for up to 17 cycles 
• Glofitamab and polatuzumab vedotin 
  • glofitamab as an infusion into the vein on Days 8 and 15 for the first 21-day cycle, and then every 3 weeks (Cycles 2–12)
  • polatuzumab vedotin as an infusion into the vein on Day 2 of the first 21-day cycle, and then every 3 weeks (Cycles 2–6)

Everyone will also be given a pre-treatment drug called ‘obinutuzumab’ as an infusion into the vein 1 week before they are given glofitamab. This is to reduce the risk of a side effect called ‘cytokine release syndrome’. Participants may also receive tocilizumab as an infusion into the vein if they experience cytokine release syndrome during the clinical trial. 

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 side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side 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 side effects of glofitamab, atezolizumab, obinutuzumab, polatuzumab vedotin and tocilizumab, and possible side effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known side effects of infusions into the vein (intravenous infusions). 

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.