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Bemcentinib Plus Pembrolizumab for Mesothelioma

From WikiMesothelioma — Mesothelioma Knowledge Base
MIST3: Bemcentinib + Pembrolizumab
Trial MiST arm 3 (NCT03654833)[1]
Phase Phase IIa, single arm, open label[2]
Patients 26, relapsed mesothelioma[1]
Drugs Bemcentinib (oral AXL inhibitor) + pembrolizumab (PD-1 antibody)[2]
Primary endpoint Disease control at 12 weeks: 12 of 26 (46.2%)[1]
Status Registry record completed, with results posted[1]

Executive Summary

Bemcentinib plus pembrolizumab was tested in MIST3, one arm of the MiST umbrella trial for relapsed mesothelioma. Bemcentinib blocks AXL, a receptor tyrosine kinase the investigators describe as a putative resistance factor to immune checkpoint blockade, and pembrolizumab blocks PD-1.[2] In 26 patients, 12 (46.2%) had disease control at 12 weeks, which met the trial's primary endpoint.[1][3]

MIST3 had no comparison arm. Its own investigators call it "a single arm phase II clinical trial, designed with the goal of identifying a potential signal of efficacy," and say confirming efficacy would require a randomised phase III trial.[2] The efficacy results were first reported in a 2023 conference abstract.[3] A September 2026 preprint added the full report and tumour, blood and gut-microbiome analyses. That preprint has not been peer reviewed.[2]

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At a Glance

  • What it is: Bemcentinib (AXL inhibitor) plus pembrolizumab (PD-1 inhibitor), tested as arm 3 of the MiST trial[1]
  • Who was treated: 26 patients whose mesothelioma had progressed after first-line pemetrexed with cisplatin or carboplatin, and who had not had immune checkpoint blockade[2]
  • Primary result: Disease control at 12 weeks in 12 of 26 patients (46.2%)[1]
  • At 24 weeks: Disease control in 10 of 26 patients (38.5%)[3]
  • Tumour shrinkage: Partial response in 4 of 26 patients (15.4%); all responses were partial[3]
  • Side effects: Grade 3 adverse events in 14 of 26 patients (53.9%) in the 2026 report; none at grade 4 or 5[2]
  • Design limit: Single arm, with no control group, so the results cannot show the combination works better than other options[2]
  • Newest data: A 2026 preprint links response to neutrophil-related tumour biology and gut bacteria. The authors call these findings exploratory, and the preprint has not been peer reviewed[2]

Key Facts

Measure Result Source
Disease control at 12 weeks (primary endpoint) 12 of 26 (46.2%) Trial registry results[1]
Disease control at 24 weeks 10 of 26 (38.5%) 2023 abstract; registry[3][1]
Objective response at 24 weeks 4 of 26 (15.4%), all partial responses 2023 abstract; registry[3][1]
Progressive disease 11 of 26 (42.3%) 2026 preprint[2]
Grade 3 or higher adverse events 38% in the 2023 abstract; 14 of 26 (53.9%) in the 2026 preprint Both reports, as published[3][2]
Treatment-related deaths None reported 2023 abstract[3]
Most common side effect Fatigue, in 12 of 26 (46%)[3] 2023 abstract[3]

What is the MIST3 trial?

MiST (Mesothelioma Stratified Therapy) is a multi-arm phase IIa trial for relapsed mesothelioma, built to evaluate targeted therapies quickly.[1] Its registry record lists five arms: rucaparib (MiST1), abemaciclib (MiST2), pembrolizumab with bemcentinib (MiST3), atezolizumab with bevacizumab (MiST4), and dostarlimab with niraparib (MiST5).[1] MiST2 is covered on the pleural mesothelioma page.

MIST3 was run at three UK centres: the University Hospitals of Leicester, the Northern Centre for Cancer Care in Newcastle upon Tyne, and The Christie in Manchester.[2]

Who was eligible?

Patients were eligible if their mesothelioma had progressed after at least one course of prior systemic treatment that included standard first-line pemetrexed with either cisplatin or carboplatin.[2] The investigators describe the group as immune checkpoint blockade–naive: none had already received immunotherapy of this kind.[2]

That matters for today's patients. The investigators note that ipilimumab with nivolumab is a front-line standard of care in mesothelioma.[2] MIST3 did not test patients who had already received immune checkpoint blockade. See immunotherapy for mesothelioma and CheckMate 743 for the front-line evidence.

How was the treatment given?

Bemcentinib was taken by mouth once daily in 21-day cycles, starting with three days of 400 mg and then 200 mg once daily from day 4.[2] Pembrolizumab was given into a vein at a fixed dose of 200 mg on day 1 of each 21-day cycle. The two drugs were given together for 24 weeks.[2]

What were the results?

The primary endpoint was disease control at 12 weeks, judged on scans read with modified RECIST criteria.[2] Disease control counts stable disease as well as tumour shrinkage; in the 2023 abstract, 57.7% of patients had stable disease.[3] Twelve of 26 patients (46.2%) reached it, which met the endpoint.[1][3]

  • Disease control at 24 weeks: 10 of 26 (38.5%)[3]
  • Partial response: 4 of 26 (15.4%)[2]
  • Progressive disease: 11 of 26 (42.3%)[2]
  • Not evaluable on scans: 3 of 26 (11.5%), because early clinical progression and symptoms prevented a repeat CT[2]

The investigators chose the 12-week mark because a 12-week disease control rate of 50% would roughly double the expected progression-free survival seen in the placebo group of an earlier phase III trial in relapsed mesothelioma.[2]

Two reports, two side-effect figures

The two published reports of these 26 patients give different rates of serious side effects. The 2023 abstract says grade 3 or higher toxicities "affected 38% of pts" with no treatment-related deaths.[3] The 2026 preprint reports grade 3 adverse events in 14 of 26 patients (53.9%) and none at grade 4 or 5.[2] The preprint is the later and fuller report. Neither source explains the difference, and this page does not try to.

What did the 2026 preprint add?

In September 2026 the investigators posted a full report on medRxiv. It has not been certified by peer review.[2] Beyond the efficacy results, it reports laboratory analyses of tumour biopsies, blood and stool samples:[2]

  • Patients who responded showed greater loss of NF2, stronger immune-response signalling, and more epithelial–mesenchymal transition. That transition was lower in biopsies taken when the drugs stopped working.[2]
  • Neutrophil-related gene programmes in the tumour were associated with response.[2]
  • Gut bacteria, measured by 16S rRNA sequencing in 21 patients, differed between responders and non-responders.[2]

These are associations in a small group, not proof of cause. The authors write that the translational analyses "should therefore be considered exploratory," and that their findings "support a hypothesis linking gut microbiota composition, neutrophil-associated tumour biology and response to AXL-PD1 inhibition."[2]

What does MIST3 mean for patients?

MIST3 found a signal worth testing further, not a new standard treatment. The trial was small and had no comparison group, and its investigators say a randomised phase III trial would be needed to confirm efficacy.[2] It also enrolled only people who had not yet had immune checkpoint blockade.[2]

For people with relapsed mesothelioma, the practical step is to ask a mesothelioma specialist about clinical trials. See mesothelioma clinical trials and finding a mesothelioma clinical trial.

Frequently Asked Questions

Is bemcentinib with pembrolizumab a standard mesothelioma treatment?

MIST3 does not establish it as one. It was tested in one small, single-arm phase IIa trial. The investigators say a randomised phase III trial would be needed to confirm efficacy.[2]

How many patients benefited in MIST3?

Twelve of 26 patients (46.2%) had disease control at 12 weeks, and 4 of 26 (15.4%) had a partial response, meaning their tumour shrank by a set amount.[1][2]

What does the gut bacteria finding mean?

Not yet anything a patient can act on. The authors describe the gut-microbiome and neutrophil findings as exploratory and as supporting a hypothesis. They come from a preprint that has not been peer reviewed.[2]

Why do the side-effect numbers differ between reports?

The 2023 abstract reported grade 3 or higher toxicities in 38% of patients. The 2026 preprint reports grade 3 adverse events in 14 of 26 (53.9%).[3][2] Neither source explains the difference.

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Mesothelioma Stratified Therapy (MiST): A Stratified Multi-arm Phase IIa Clinical Trial to Enable Accelerated Evaluation of Targeted Therapies for Relapsed Malignant Mesothelioma, ClinicalTrials.gov, NCT03654833. Results posted.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 Tumour extrinsic neutrophil regulation in mesothelioma correlates with responsiveness to AXL and PD1 inhibition in MIST3, a phase IIA clinical trial., Fennell DA, Dzialo J, Zhang M, et al., medRxiv, 2026. Preprint posted September 25, 2026; not certified by peer review. doi:10.64898/2026.09.22.26363540.
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 Bemcentinib and pembrolizumab in patients with relapsed mesothelioma: MIST3, a phase IIa trial with cellular and molecular correlates of efficacy., Krebs MG, Branson A, Barber S, et al., J Clin Oncol, 2023. 41(16_suppl):8511.
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