ArticleJournal for immunotherapy of cancer2026
Biomarkers of activity from a phase I study of cergutuzumab amunaleukin in patients with advanced solid tumors.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02004106 (An Open-Label, Multi-Center, Dose-Escalation, Phase I Study With an Expansion Phase, to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6895882, an Immunocytokine, Consisting of a Variant of Interleukin-2), which is not on this map. Cited by 1 paper.
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.
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.
An Open-Label, Multi-Center, Dose-Escalation, Phase I Study With an Expansion Phase, to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6895882, an Immunocytokine, Consisting of a Variant of Interleukin-2 (IL-2v) Targeting Carcinoembryonic Antigen (CEA) Administered Intravenously, in Patients With Advanced and/or Metastatic Solid Tumors
Who cites it
1 citing paper in PubMed.
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCergutuzumab amunaleukin (CA) is an immunocytokine comprising an anticarcinoembryonic antigen (CEA) linked to an interleukin-2 (IL-2) variant. CA does not bind to CD25 (IL-2 receptor α) and was designed to maintain the T and natural killer (NK) cell stimulatory effect, while avoiding stimulating effects on regulatory T cells (Tregs). In mouse models, CA previously demonstrated superior tumor targeting to CEA surface expression-positive (CEA+) tumors and increased CD8+ T cells and NK cell numbers in peripheral blood and tumor tissue when compared with wild-type IL-2. We present biomarker data from the first-in-human, open-label, multicenter, phase I, dose-escalation study investigating CA in patients with metastatic/unresectable CEA+ solid tumors (NCT02004106).
methodsPatients received ascending doses of CA intravenously weekly (qw: 6/10/20 mg) or every 2 weeks (q2w: 10/20/30/40 mg). Flow cytometry determined absolute numbers/mL of CD4+ and CD8+ T cells, NK cells, macrophages/monocytes, Tregs, and B cells and their expression of activation and proliferation markers in circulation. Sequential pretreatment and on-treatment paired tumor biopsies were studied by flow cytometry, multicolor immunohistochemistry, and bulk RNA sequencing. Antitumor activity was used for correlative studies.
resultsBiomarker data were collected from 55 patients. After treatment, peripheral blood samples showed increased proliferating NK cells, CD8+ T cells, and CD4+ T cells, without an apparent dose effect. Levels of circulating soluble CD25 increased in patients with intermediate/high CA doses on-treatment; levels of cytokines, such as tumor necrosis factor, also increased with high CA dose levels. On-treatment tumor samples showed increases in total and proliferating CD8+ T cells as well as CD3+ perforin+ T cells but, importantly, not in Tregs. Notably, increases in the ratio of CD8+/CD4+ T cells were more pronounced for qw than for q2w dosing, while programmed death ligand-1-positive CD14+ cells increased, particularly for the q2w schedule. Higher on-treatment circulating levels of cytokines correlated with longer progression-free survival (PFS). Apart from the positive correlation with NK cell density, no other correlations between PFS and infiltrating immune cell populations in the tumor were observed.
conclusionsCA-induced immune pharmacodynamic effects in peripheral blood and in the tumor microenvironment without preferential Treg cell activation in patients with metastatic/unresectable CEA+ solid tumors. TRIAL REGISTRATION NUMBER: NCT02004106; BP28920.
Indexed as
Identifiers
What OpenQuestion holds
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.