# Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer

Source: https://onco.cc/key-papers/paper-cd47-colorectal-cancer-res-commun-2025/  
OnCo record `paper-cd47-colorectal-cancer-res-commun-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Patients 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).

Results: 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.

Conclusions: 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.

Significance: 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.

Indexed 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Cancer research communications
- Year: 2025
- DOI: 10.1158/2767-9764.crc-25-0332
- Authors: Lentz RW, Lang J, Pitts TM, et al.
- What it means: 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.

## Sources

- Cancer Res Commun 2025: https://doi.org/10.1158/2767-9764.crc-25-0332
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41171165/
- Europe PMC: https://europepmc.org/article/MED/41171165

## Connected records

- journals: [Cancer research communications](https://onco.cc/journals/cancer-research-communications/)
- ideas: [Engineered bacteria that live in tumours and manufacture drugs there](https://onco.cc/ideas/idea-bio2-engineered-bacteria-payloads/), [Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours](https://onco.cc/ideas/idea-moon-cold-to-hot-programme/)

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