Dataset Information

TIMEPOINT, a phase 1 study of MTL-CEBPA in combination with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumours.

ABSTRACT: Many cancer patients don’t benefit from currently-approved immune checkpoint inhibitors (ICI), suggesting that additional immunomodulation of the immunosuppressive tumour microenvironment (TME) is required. MTL-CEBPA specifically upregulates expression of master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report the safety, tolerability, pharmacokinetics, and efficacy of MTL-CEBPA in combination with pembrolizumab in patients with advanced solid tumours that typically show ICI resistance. Multimodal exploratory analyses of paired patient biopsies demonstrate biological changes associated with combination treatment of MTL-CEBPA and pembrolizumab, including increased infiltration of T cell and antigen-presenting cells supporting conversion from an immune desert towards a more immune-inflamed TME. Patients with disease stabilisation demonstrate reductions in immunosuppressive myeloid cells post-treatment. Collectively, these data support a role for MTL-CEBPA in reducing immunosuppression in the TME. This study was registered at ClinicalTrials.gov (NCT04105335). This manuscript also reports proteomic data from patients treated with MTL-CEBPA in combination with sorafenib from clinical trial, OUTREACH, accessible at ClinicalTrials.gov, number NCT02716012 and reported. Stored plasma from patients from this clinical trial were analysed using OLINK as described below.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Rose Hodgson

LAB HEAD: Bríd Ryan

PROVIDER: PXD060726 | Pride | 2025-05-07

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	OUTREACH_C1D1_inflammation_pride.csv	Csv
	OUTREACH_Olink_metadata.csv	Csv
	OlinkTarget96Inflammation-2025-01-27.csv	Csv
	TIMEPOINT_OLINK_passedQC_C1D1.csv	Csv
	TIMEPOINT_Olink_metadata.csv	Csv

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TIMEPOINT, a phase 1 study combining MTL-CEBPA with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumors.

Plummer Ruth R Sodergren Mikael H MH Hodgson Rose R Ryan Bríd M BM Raulf Nina N Nicholls Joanna P JP Reebye Vikash V Voutila Jon J Sinigaglia Laura L Meyer Tim T Pinato David J DJ Sarker Debashis D Basu Bristi B Blagden Sarah S Cook Natalie N Jeffrey Evans Thomas R TR Yachnin Jeffrey J Chee Cheng E CE Li Daneng D El-Khoueiry Anthony A Diab Maria M Huang Kai-Wen KW Pai Madhava M Spalding Duncan D Talbot Thomas T Noel Marcus S MS Keenan Bridget B Mahalingam Devalingam D Song Min-Sun MS Grosso Mélanie M Arnaud Denis D Auguste Aurelie A Zacharoulis Dimitris D Storkholm Jan J McNeish Iain I Habib Robert R Rossi John J JJ Habib Nagy A NA

Cell reports. Medicine 20250331 4

Many patients with cancer do not benefit from currently approved immune checkpoint inhibitors (ICIs), suggesting that additional immunomodulation of the immunosuppressive tumor microenvironment (TME) is required. MTL-CCAAT enhancer-binding protein alpha (CEBPA) specifically upregulates the expression of the master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report the safety, tolerability, pharmacokinetics, and efficacy of MTL-CEBPA in combination wi ...[more]

PMID: 40168999

Publication: 1/2

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