A trial looking at targeted drugs for mesothelioma (MiST)

Cancer type:

Mesothelioma

Status:

Results

Phase:

Phase 2

This trial looked at several different treatments for mesothelioma Open a glossary item that had continued to grow or had come back after chemotherapy.

MiST stands for Mesothelioma Stratified Therapy. The trial was designed to look at several new and different treatments at the same time. Some treatments were for anyone with advanced mesothelioma. Some were for people with specific gene or protein changes. There is more detail about this below.

The trial was open for people to join between 2019 and 2022. The team have published and presented results for the different groups between 2021 and 2024.

More about this trial

Mesothelioma is cancer that starts in the layer of tissue around the lungs (the pleura) or the abdomen (peritoneum). It is also called pleural mesothelioma or peritoneal mesothelioma. Pleural mesothelioma is more common than peritoneal mesothelioma.

Doctors often use chemotherapy to treat mesothelioma. But sometimes it continues to grow or comes back after treatment. When this trial was done, there were no standard treatments Open a glossary item available for people in this situation.

Researchers wanted to find out if various targeted cancer drugs could help. These treatments work by stopping the signals that mesothelioma cells use to divide and grow.

There were 5 parts to this trial. Each part looked at a different targeted treatment or treatments. All 5 parts were for people with mesothelioma that had come back after other treatment.

MiST1 looked at rucaparib for people with fewer copies than normal of the BAP1 protein or the BRCA1 gene Open a glossary item . This is called BAP1 deficiency or BRCA1 deficiency.

MiST2 looked at abemaciclib for people with fewer copies than normal of the p16ink4A gene. This is called being p16ink4A deficient or p16ink4A negative.

MiST3 looked at bemcentinib and pembrolizumab for pleural mesothelioma.

MiST4 looked at atezolizumab and bevacizumab.

MiST5 looked at niraparib and dostarlimab.

The main aims of each part of the MiST trial were to find out:

how well the treatments work
what the side effects are

Summary of results

A total of 130 people joined the MiST trial. There were 26 people in each of the 5 treatment groups.

The research team looked at how well treatment was working after about 3 months (12 weeks) and 6 months (24 weeks) of treatment. They looked at the number of people whose cancer stayed the same or got a bit better.

They also looked at the side effects for each treatment.

MiST1 (rucaparib)
The cancer stayed the same or got a bit smaller in:

15 people (58%) at 3 months
6 people (23%) at 6 months

A total of 24 out of 26 people (92%) had at least 1 side effect from treatment. Many were mild or didn’t last long. The most common of the mild side effects were sickness and extreme tiredness (fatigue).

9 out of 26 people had more severe side effects. The most common of these were:

chest (respiratory) infections
a drop in red blood cells causing tiredness and shortness of breath

We have more information about the side effects of rucaparib in our Cancer drugs section.

The trial team concluded that the side effects of rucaparib weren’t too bad. And that it may be a useful treatment for people with mesothelioma and fewer copies than normal of the BAP1 protein or the BRCA1 gene.

MiST1 led to a trial called NERO which looked at niraparib, a similar drug to rucaparib. People taking part either had niraparib or standard care Open a glossary item . The NERO trial was for people who’d had treatment for their mesothelioma, but it had started to grow again.

MiST2 (abemaciclib)
The cancer stayed the same or got a bit smaller in:

• 14 people (54%) at 3 months
• 6 people (23%) at 6 months

Most people (92%) had at least 1 side effect. Many were mild or didn’t last long. The most common of these were extreme tiredness (fatigue) and diarrhoea.

A small number of people had at least 1 side effect that was more severe. These included:

a drop in blood clotting cells (platelets)
an increased level of a liver protein (enzyme ) called alanine aminotransferase
a low level of white blood cells and severe infection (neutropenic sepsis)
a chest infection
diarrhoea

We have more information about the side effects of abemaciclib in our Cancer drugs section.

The team concluded that abemaciclib may be a useful treatment for advanced mesothelioma with fewer copies than normal of the p16ink4A gene. They suggest more trials are done.

MiST3 (bemcentinib and pembrolizumab)
The cancer stayed the same or got a bit smaller in:

12 people (46%) at 3 months
10 people (38%) at 6 months

A total of 24 out of 26 people (92%) taking part had a least 1 side effect. Many of these were mild or didn’t last long. The most common were fatigue and feeling sick.

10 people (38%) had a more severe side effect. The most common of these were:

fever
inflammation of the liver (autoimmune hepatitis)
a fall in the number of blood clotting cells (platelets)

We have more information about pembrolizumab in our Cancer drugs section.

The team concluded that the combination of bemcentinib and pembrolizumab may be useful for advanced mesothelioma. They suggest more trials are done.

MiST4 (atezolizumab and bevacizumab)
The cancer stayed the same or got a bit smaller in:

13 people (50%) at 3 months
7 people (27%) at 6 months

A total of 23 out of 26 people (88%) taking part had a least 1 side effect. Many of these were mild or didn’t last long. The most common were fatigue and weight loss.

8 people (31%) had a more severe side effect. The most common of these were:

vomiting
liver problems

We have more information about the side effects of atezolizumab and bevacizumab in our Cancer drugs section.

The team concluded that atezolizumab and bevacizumab could be a useful treatment for mesothelioma, but the results were a bit mixed.

The team also looked at the bacteria in the gut of people taking part. This is called the gut microbiome Open a glossary item or microbiota.

They found that the amount and type of bacteria in the gut can affect how the immune system responds to treatment. And this can affect how well treatment works. The team suggest further research is needed to see if treatment may work better if people change their diet.

MiST5 (niraparib and dostarlimab)
The cancer stayed the same or got a bit smaller in:

17 people (65%) at 3 months
8 people (31%) at 6 months

A total of 24 out of 26 people (92%) taking part had a least 1 side effect. Many of these were mild or didn’t last long. The most common were fatigue and feeling sick.

9 people (35%) had a more severe side effect. The most common of these were:

fever
chest infection

We have more information about the side effects of niraparib and dostarlimab in our Cancer drugs section.

The team concluded that niraparib and dostarlimab could be a useful treatment for advanced mesothelioma.

Summary of results for all groups
The graphs below show how well treatment worked for all 5 groups.

MIST Trial results - Bar chart showing percentage of people whose cancer was the same or a bit better at 3 months

MIST Trial results - Bar chart showing percentage of people whose cancer was the same or a bit better at 6 months

Overall conclusion
The trial team concluded that the treatments in this trial didn’t cause too many side effects. And that they might be useful for mesothelioma that has come back after other treatment.

The results of the different treatment combinations used in MiST are promising. And this trial has added a lot to our knowledge of mesothelioma and how best to treat it. Other trials are being done or are planned to find out more.

More detailed information
There is more information about this research in the references below.

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial
Dean A Fennell and others
The Lancet Respiratory Medicine, 2021. Volume 9, issue 6, pages 593-600.

Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial
Dean A Fennell and others
The Lancet Oncology, 2022. Volume 23, issue 3, pages 374-381.

Bemcentinib and pembrolizumab in patients with relapsed mesothelioma: MIST3, a phase IIa trial with cellular and molecular correlates of efficacy.
Matthew G Krebs and others
Journal of Clinical Oncology, 2023. Volume 41, Number 16, supplement.
Presented as the 2023 ASCO Annual Meeting.

Atezolizumab and bevacizumab in patients with relapsed mesothelioma: MIST4—a phase IIa trial with cellular and molecular correlates of efficacy.
Dean A Fennel and others
Journal of Clinical Oncology, 2022. Volume 40, Number 16, supplement.
Presented at the 2022 ASCO Annual Meeting.

A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma
Min Zhang and others
Nature Communications, 2024. Volume 15, issue 1, article number 7187.

Niraparib and dostarlimab efficacy in patients with platinum-sensitive relapsed mesothelioma: MIST5, a phase IIa clinical trial.
Dean A Fennell and others
Journal of Clinical Oncology, 2024. Volume 42, Number 16, supplement.
Presented at the 2024 ASCO Annual Meeting.

Where this information comes from
We have based this summary on the information in the articles above. Some of them have been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in medical journals. We have not analysed the data ourselves.