A trial looking at copanlisib to treat non-Hodgkin lymphoma (CHRONOS-4)

Cancer type:

Blood cancers

Lymphoma

Non-Hodgkin lymphoma

Status:

Results

Phase:

Phase 3

This trial looked at adding copanlisib to rituximab and chemotherapy. It was for people with certain types of non-Hodgkin lymphoma that had come back after treatment.

The trial was open for people to join between 2016 and 2020. The team published the results in 2021 and 2024.

More about this trial

The trial was for people who had one of the following types of low grade (slow growing) non-Hodgkin lymphoma (NHL):

follicular lymphoma
small lymphocytic lymphoma
lymphoplasmacytic lymphoma including Waldenstrom's macroglobulinemia
marginal zone lymphoma

When this trial was done, chemotherapy and a drug called rituximab were standard treatments Open a glossary item for NHL that had come back. Rituximab is a type of targeted cancer drug.

Copanlisib was a newer type of targeted cancer drug Open a glossary item at the time of this trial. Researchers knew from earlier research that it could be a useful treatment for NHL that had come back. This was compared to having rituximab and chemotherapy. So the trial team did this trial to find out more.

There were 2 parts to this trial:

part 1 looked at the best dose of copanlisib to have with rituximab and chemotherapy
part 2 tested the best dose of copanlisib in more people

In part 2, everyone was put into a treatment group at random:

half had rituximab, chemotherapy and a dummy drug (placebo )
half had rituximab, chemotherapy and copanlisib

The main aims of this phase 3 trial were to:

find the best dose of copanlisib to have with rituximab and chemotherapy
see if adding copanlisib to rituximab and chemotherapy improves treatment
see what the side effects are

Summary of results

The team found that adding copanlisib to rituximab and chemotherapy didn’t improve treatment. It didn’t increase the length of time before the cancer started to grow again.

Results for part one
27 people had copanlisib with rituximab and chemotherapy. The aim was to find the best dose of copanlisib to give. The first few people had the lowest dose of
copanlisib. If they didn’t have any side effects the next few people had a higher dose and so on until they found the best dose to give. This is called a dose escalation study. The team found the best dose of copanlisib to give with the fewest side effects.

Results for part two
524 people joined this part of the trial:

262 were in the rituximab, chemotherapy and dummy drug group
262 were in the rituximab, chemotherapy and copanlisib group

The team followed everyone up for 47 months. They looked at how long it was before the cancer started to grow again. This was:

33.3 months in the rituximab, chemotherapy and dummy drug group
32.9 months in the rituximab, chemotherapy and copanlisib group

The team also looked at:

whose cancer had either gone away completely or shrunk
how long people lived

They found no difference in the 2 different groups.

Side effects
Most people had at least one side effect. Some of them were mild and didn’t last long.

Some people had side effects that were more severe. The team looked at the number of people who had more severe side effects. They found it was:

54 people (21%) in the rituximab, chemotherapy and dummy drug group
161 people (61%) in the rituximab, chemotherapy and copanlisib group

The most common severe side effect of rituximab, chemotherapy and the dummy drug included:

a drop in the number of certain types of white blood cells, including neutrophils

The most common severe side effects of rituximab, chemotherapy and copanlisib included:

high levels of sugar in the blood
high blood pressure
a drop in the number of certain types of white blood cells, including neutrophils
pneumonia

Researchers can class a side effect as serious for a number of reasons, including if:

the person has to go to hospital because of it
it is particularly important for the specific treatment in the trial

People in the rituximab, chemotherapy and copanlisib group had more serious side effects. The most common included:

pneumonia
high temperatures
a drop in the number of blood cells called neutrophils with a temperature

3 people in the rituximab, chemotherapy and copanlisib group died because of side effects related to treatment. No one in the rituximab, chemotherapy and the dummy drug group died because of side effects.

The team looked at the number of people who had to stop treatment permanently because of side effects related to treatment: This was:

15 people (6%) in the rituximab, chemotherapy and dummy drug group
57 people (22%) in the rituximab, chemotherapy and copanlisib group

They also looked at the number of people whose treatment was interrupted or delayed due to side effects. This was:

169 (65.8%) people in the rituximab, chemotherapy and dummy drug group
215 (81.7%) people in the rituximab, chemotherapy and copanlisib group

Conclusion
The team found that adding copanlisib to rituximab and chemotherapy didn’t improve treatment. They also found that the side effects of adding copanlisib to rituximab and chemotherapy were much worse.

Based on these findings and other similar trials, the team say there won’t be any more trials looking at copanlisib.

Sometimes trials show a different treatment isn’t useful for a particular type or stage Open a glossary item of cancer. But these trials still add to our knowledge and understanding of cancer and how to treat it.

Where this information comes from
We have based this summary on the information in the articles below. We have not analysed the data ourselves.

The first two articles have been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in medical journals. Please note, the information in these is not in plain English. It has been written for healthcare professionals and researchers.

Feasibility of Combining the Phosphatidylinositol 3-Kinase Inhibitor Copanlisib With Rituximab-Based Immunochemotherapy in Patients With Relapsed Indolent B-cell Lymphoma
M Matasar and others
Clinical Lymphoma, Myeloma and Leakemia, 2021. Volume 21, issue 11, pages 886 to 894.

CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma
P Zinzani and others
Blood advances, 2024. Volume 8, issue 8, pages 4866 – 4876.

The third link is to a lay summary that has been written by the trial team at the pharmaceutical company.