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Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial

GSE322664 Homo sapiens (human) RNA-seq (gene expression) 41 samples Submitted 2026/03/02 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 41 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Ewing sarcomaThis series is part of our curated briefing on it.
Samples
41 samples: 14 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trialNature medicine · 2026
Summary (written by the submitters)
Ewing sarcoma (ES) is a bone and soft tissue sarcoma that is absolutely dependent on the EWS::FLI1 transcription factor for cell survival. No compound has been shown to reverse EWS::FLI1 activity in patients, and outcomes for relapsed patients remain poor. Trabectedin above a threshold concentration reverses the activity of EWS::FLI1 and is potentiated by low-dose irinotecan in vivo.
Read the full summary ↓
This open-label phase 1/2 trial of trabectedin with irinotecan (SARC037) enrolled 37 relapsed/refractory patients with ES. The primary objectives were to determine the safety, tolerability, recommended phase 2 dose (RP2D; phase 1) and objective response rate (ORR; phase 2) of trabectedin administered as a 1-hour infusion in combination with low-dose irinotecan in patients with ES. The secondary objectives were to determine the progression-free survival (PFS), 6-month PFS, duration of response and 18F-fluorothymidine positron emission tomography (18F-FLT PET) avidity of ES tumors. The RP2D was trabectedin 1.0 mg m−2 over 1 hour (day 1) and irinotecan 25 mg m−2 (days 2 and 4) of a 21-day cycle. Toxicities were manageable with grade 3 or higher toxicities (>15%) of myelosuppression and alanine aminotransferase elevations at RP2D. The phase 2 ORR was 33% (39%, including RP2D phase 1 patients), and 6-month PFS was 48%. Transcriptional profiling demonstrated reversal of the EWS::FLI1 transcriptome in tumors from a subset of patients. Additional correlative objectives captured molecular profiling, circulating tumor DNA levels, pharmacokinetics and 18F-FLT PET avidity. Here we provide the basis for further development of trabectedin/irinotecan for patients with ES by the international cooperative groups. ClinicalTrials.gov: NCT04067115.
Published in
Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial
Grohar PJ, Heise R, Wedekind MF et al. · Nature medicine 2026 · PMID 41991689 · doi:10.1038/s41591-026-04340-7
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE322664_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1430872 and SRA study SRP680353. Searching any of these in the dataset finder brings you back here.

Study design
14 conditions, mostly in triplicate
RNA-seq from 003 Post Treatment ×3 RNA-seq from 016 Post Treatment ×3 RNA-seq from 013 Pre Treatment ×3 RNA-seq from 025-031 Post Treatment ×3 RNA-seq from 025-031 Pre Treatment ×3 RNA-seq from 032 Pre Treatment ×3 RNA-seq from 032 Post Treatment ×3 RNA-seq from 038 Post Treatment ×3 +8 more

Supports a between-group comparison across 39 samples.

How we read this: 14 replicated groups read from 41 sample titles; they account for 39 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 1 more — browse all 41 samples with per-sample file links →

More Ewing sarcoma datasets

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.