{"entity":{"id":"paper-cd47-colorectal-cancer-res-commun-2025","kind":"paper","name":"Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on CD47 in Colorectal cancer, in Cancer research communications (2025), one of the most cited Europe PMC records with CD47 in its title.","summary":"Purpose: In this preclinical human immune system patient-derived xenograft (HIS-PDX) model and phase II clinical trial, we assessed evorpacept (anti-CD47 engineered fusion protein with inactive Fc), cetuximab, and pembrolizumab (triple therapy) in microsatellite-stable (MSS) colorectal cancer.\n\nPatients and methods: HIS BALB/c-Rag2nullIl2rγnullSirpαNOD mice with PDXs were treated with triple therapy or its components. Patients with refractory MSS colorectal cancer were treated with triple therapy in a safety run-in (stage 1) followed by expansion (stage 2, planned N = 42). The co-primary objectives were to determine the recommended dose of evorpacept and objective response rate (vs. historic control).\n\nResults: In HIS-PDX mice, triple therapy decreased the growth of MSS colorectal cancer tumors and increased tumor-infiltrating CD8+ T cells. Sixteen patients were treated on the clinical trial across two evorpacept dose levels: N = 12 in stage 1 and N = 4 in stage 2. Trial enrollment was terminated early because of safety concerns (one treatment-related grade 5 event each of hemophagocytic lymphohistiocytosis and cytokine release syndrome). Otherwise, the adverse event profile was as expected. Among all patients, the objective response rate was 6.3%; formal hypothesis testing was not performed. The disease control rate was 12.5%, the median progression-free survival was 2.3 months, and the median overall survival was 10.9 months. Blood- and tumor-based clinical trial correlative analyses identified innate and adaptive immune system activation.\n\nConclusions: Whereas triple therapy demonstrated evidence of efficacy in refractory MSS colorectal cancer, safety concerns halted enrollment. Further investigation is necessary to determine the optimal use of CD47-targeted therapies in MSS colorectal cancer.\n\nSignificance: Evorpacept, cetuximab, and pembrolizumab demonstrated antitumor activity in a preclinical HIS-PDX model and clinical trial in refractory MSS colorectal cancer; however, immune-related adverse events prompted early termination of study enrollment. Evidence of innate and adaptive antitumor immune activation was identified. The role of SIRPα/CD47 blockade in the treatment of MSS colorectal cancer needs to be further elucidated in future trials.\n\nIndexed on Europe PMC as PubMed record 41171165 (DOI 10.1158/2767-9764.crc-25-0332). Its title names CD47 and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"Engineered bacteria that live in tumours and manufacture drugs there\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res Commun 2025","url":"https://doi.org/10.1158/2767-9764.crc-25-0332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41171165/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41171165"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research-communications"],"dependsOn":[],"notes":[],"journal":"Cancer research communications","year":2025,"doi":"10.1158/2767-9764.crc-25-0332","pmid":"41171165","authors":"Lentz RW, Lang J, Pitts TM, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD47 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD47 in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-cd47-colorectal-cancer-res-commun-2025/","neighbours":{"journal":[{"id":"cancer-research-communications","kind":"journal","name":"Cancer research communications","route":"/journals/cancer-research-communications/"}],"idea":[{"id":"idea-bio2-engineered-bacteria-payloads","kind":"idea","name":"Engineered bacteria that live in tumours and manufacture drugs there","route":"/ideas/idea-bio2-engineered-bacteria-payloads/"},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","route":"/ideas/idea-moon-cold-to-hot-programme/"}]}}