Evidence map›Paper›PMID 40888040›Full record

ArticleNeuro-oncology2025

Phase IB study of Avelumab and whole brain radiotherapy in patients with leptomeningeal disease from solid tumors: Results and molecular analyses.

Yolanda Piña, Vincent Law, Solmaz Sahebjam, Nam Tran, Navya Siddarajappa, Jiannong Li, Qianxing Mo, Manali S Phadke, John Arrington, Robert Macaulay and 7 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03719768 (Phase IB Study of Avelumab With Radiotherapy in Patients With Leptomeningeal Disease), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03719768 phase1completednot on this map

Phase IB Study of Avelumab With Radiotherapy in Patients With Leptomeningeal Disease

TypeinterventionalSponsorH. Lee Moffitt Cancer Center and Research InstituteRan2019 to 2024Enrolled16ConditionsLeptomeningeal Metastases, Leptomeningeal DiseaseArmsAvelumab, Whole Brain Radiotherapy
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Yolanda PiñaDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.ORCID 0000-0003-1383-5704
Vincent LawORCID 0000-0002-8569-1378
Solmaz SahebjamDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.ORCID 0000-0001-9930-9937
Nam TranDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Navya SiddarajappaDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Jiannong LiDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Qianxing MoDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.ORCID 0000-0002-0021-7694
Manali S PhadkeDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
John ArringtonDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Robert MacaulayDepartment of Radiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Sepideh MokhtariDepartment of Neuropathology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Brittany EverndenDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Kamran A AhmedDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Inna SmalleyDepartment of Radiation-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.ORCID 0000-0002-6796-9145
Michael YuDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Keiran S M SmalleyDepartment of Radiation-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Peter A ForsythDepartment of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.ORCID 0000-0002-3756-8594

Funding

Targeting the suppressive immune microenvironment in leptomeningeal melanoma metastasesR21CA256289 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SMALLEY, KEIRAN · 2021 to 2022
$420k
Florida Department of Health Bankhead-Coley Program 24B04H. Lee Moffitt Cancer Center & Research InstituteMerck KGaANCI Comprehensive Cancer P30-CA076292NCI NIH HHS R21CA256289Pfizer
6 · The paper itself

Abstract

backgroundLeptomeningeal disease (LMD) from solid tumors has a dismal prognosis, even following treatment with anti-PD-1 therapy. We performed a phase IB study evaluating the safety of Avelumab with whole brain radiotherapy (WBRT) in LMD (NCT03719768).

methodsFifteen patients were enrolled with LMD from breast, lung, nasopharyngeal, ovarian, and pancreatic tumors. Patients were treated with Avelumab with WBRT, with the first infusion of Avelumab starting 14 days pre-WBRT and continuing during and post-WBRT for up to 5 cycles. Primary endpoints were safety and 3-month OS (OS3). Secondary endpoints included assessment of immune cells in the cerebrospinal fluid (CSF) using single-cell RNA-sequencing (scRNA-Seq) pre- and post-last treatment of Avelumab.

resultsDLTs occurred in 2 patients, ie, adrenal insufficiency, hypothyroidism, and pneumonitis. Treatment-related toxicities occurred in 5 patients with grade 1/2 and 5 patients with grade 3/4. Immune-related adverse events occurred in 5 patients with grade 1/2 and 3 patients with grade 3/4. The OS3 was 67% (10 of the 15; 95% CI: 38%-84%). Median-OS was 3.85 months (95% CI: 0.9-34.4 months) and median-PFS was 3.85 months (95% CI: 0.9-12.1 months). scRNA-Seq analysis of CSF pre- and post-last-treatment showed Avelumab + WBRT stimulated an adaptive immune response associated with a decrease in regulatory T cells (Tregs), among other changes in the expression of immune checkpoints on CD8 + T cells and macrophages.

conclusionsThe combination of Avelumab and WBRT is safe and demonstrates activity in patients with LMD. The identification of high levels of Tregs and macrophages in the CSF of LMD patients offers future avenues for therapeutic development.

Indexed as

Antibodies, Monoclonal, HumanizedCranial IrradiationMeningeal NeoplasmsNeoplasmsAdultAgedBiomarkers, TumorFemaleFollow-Up StudiesHumansMaleMiddle AgedPrognosisAntibodies, Monoclonal, HumanizedavelumabBiomarkers, TumorAvelumabimmunotherapyleptomeningeal diseaseradiotherapy

Identifiers

PMID40888040
PMCPMC12916732

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.