ArticleCancer research communications2022
Bintrafusp alfa, an anti-PD-L1:TGF-β trap fusion protein, in patients with ctDNA-positive, liver-limited metastatic colorectal cancer.
Article in Cancer research communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- An international phase II trial and immune profiling of SBRT and atezolizumab in advanced pretreated colorectal cancer.Molecular cancer · 2024Trial
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Macrophage Polarization as a Target for Colorectal Cancer Treatment Optimization: A Systematic Review.Cancers · 2026Review
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- Clinical and translational results from the phase II ABACO trial evaluating the activity of cabozantinib in pretreated patients with metastatic colorectal cancer.ESMO gastrointestinal oncology · 2026Article
- Rewiring tumor cytokine networks to enhance immune checkpoint blockade: mechanisms, engineering, and clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- A Bioimaging Study ofMolecular imaging and biology · 2026Article
- Spatial immune archetypes in gastric and colorectal cancer: a proposed conceptual framework for immunotherapy resistance and therapeutic remodeling.Frontiers in immunology · 2026Review
- Review
- SMAD4 Deficiency Promotes Pancreatic Cancer Progression and Confers Susceptibility to TGFβ Inhibition.Cancer research · 2025Article
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- 68Ga-FAPI PET imaging monitors response to combined TGF-βR inhibition and immunotherapy in metastatic colorectal cancer.The Journal of clinical investigation · 2024Article
- Mismatch repair-proficient tumor footprints in the sands of immune desert: mechanistic constraints and precision platforms.Frontiers in immunology · 2024Review
- Immunotherapy in Gastrointestinal Cancers.Cancer treatment and research · 2024Review
- Cancer cell plasticity during tumor progression, metastasis and response to therapy.Nature cancer · 2023Review
- Review
- Review
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
Background: Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) CRC, increased TGF-β signaling results in exclusion of anti-tumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor ("TGF-β trap") and anti-PD-L1 antibody. Methods: Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t-tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Results: Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 AE. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared to a historical cohort, patients administered BA developed more metastases (15 versus 2, p=0.005) and greater tumor volumes (9 cm vs 2 cm, p=0.05). Conclusions: Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGF-β and PD-L1 inhibition.
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Registered trials
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