Purpose of trial
The aim of this trial is to establish the safety, and work out the best dose, of a combination of atezolizumab and a new treatment called RO7082859 for people with B-cell non-Hodgkin lymphoma that has come back (relapsed) or not responded (refractory) after treatment.
Everybody in this study has the same treatment.
- You have one dose of obinutuzumab.
- You have RO7082859 every 3 weeks, starting 1 week after your dose of obinutuzumab.
- You have atezolizumab every 3 weeks from the second treatment cycle onwards (on the same day as RO7082859 but starting 4 weeks after your dose of obinutuzumab).
All the treatments are given intravenously (though a drip into a vein). Each cycle of treatment is 3 weeks. You have up to 17 cycles of treatment. Due to the potential for side effects, you are admitted to hospital to have the first and second cycles of treatment so you can be monitored closely for side effects. For subsequent cycles, you have treatment as an outpatient.
Obinutuzumab is an antibody therapy that binds to a protein called CD20 on the surface of B cells. This attracts immune system cells to destroy the B cells. In this trial, it is used to reduce the side effects and toxicities of the bispecific antibody (RO7082859).
RO7082859 is a type of antibody called a ‘T-cell bispecific antibody’ (TCB). Most antibody treatments attach to one target protein but TCBs can attach to two targets on different cells (they are ‘bispecific’).
RO7082859 attaches to a protein called CD20 on B cells and to a protein called CD3 on T cells. This brings your healthy T cells into close contact with the cancerous B cells, boosting your immune response to the cancer.
Atezolizumab is a checkpoint inhibitor that stops lymphoma cells hiding from your immune system. This allows your immune system to recognise and kill the lymphoma cells. It is expected that this may enhance the activity of the bispecific antibody.
Who can enter
Your consultant can give you advice on whether you might be suitable for this trial.
Around 140 people are needed for this trial.
You may be able to enter if:
- You have a B-cell non-Hodgkin lymphoma that is likely to make a protein called CD20. Most B-cell lymphomas make this protein. Your doctor can give you more information.
- You have previously had at least one course of treatment for your lymphoma.
- No other treatment options are suitable for you.
- Your lymphoma is measurable by the tests used in the trial.
- You are well enough to take part in the trial.
- Your blood and other health test results are satisfactory.
- You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
- You are 18 or over.
You won’t be able to enter if:
- You have chronic lymphocytic leukaemia (CLL), Burkitt lymphoma, or lymphoplasmacytic lymphoma.
- Your lymphoma has not responded to previous treatment with obinutuzumab on its own.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
- You had serious immune-related side effects from your previous treatment. Your doctor can tell you if this is the case.
- Your lymphoma is, or has been, in your central nervous system (CNS; brain and spinal cord).
- You have ever had any other diseases affecting your CNS.
- You have an infection, heart or lung disease or immune deficiency.
- You have an autoimmune disease (except underactive thyroid if it is controlled, type 1 diabetes if it is controlled on insulin, or autoimmune skin conditions if they affect less than 10% of your body and are well controlled on low strength steroid creams).
- You’ve had surgery in the last 4 weeks.
- You’ve ever had an organ transplant or an allogeneic (donor) stem cell transplant.
- You’ve had an autologous (self) stem cell transplant within the last 100 days.
- You are taking or have taken certain other drugs.
- You have had a live, attenuated vaccine within the last 4 weeks or are likely to need one within 5 months of finishing the study treatment.
- You have HIV, hepatitis C or hepatitis B.
- You are pregnant or breastfeeding.
- Any of the study drugs are not suitable for you.
More information about this trial is available at clinicaltrials.gov/ct2/show/NCT03533283