ArticleJournal for immunotherapy of cancer2023
Phase 1 first-in-human study of dalutrafusp alfa, an anti-CD73-TGF-β-trap bifunctional antibody, in patients with advanced solid tumors.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03954704 (A Phase 1a/1b Study of GS-1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, as Monotherapy or in Combination With a Chemotherapy Regimen in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 27 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.
A Phase 1a/1b Study of GS-1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, as Monotherapy or in Combination With a Chemotherapy Regimen in Subjects With Advanced Solid Tumors
Who cites it
27 citing papers in PubMed, 29 citations in OpenAlex.
- Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Enhanced antitumor efficacy of combined targeting of adenosine ACancer immunology, immunotherapy : CII · 2026Article
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- IL7-TBRII, a Dual Cytokine Modulator Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis.Immune network · 2025Article
- Updates on radiotherapy-immunotherapy combinations: Proceedings of 8th Annual ImmunoRad Conference.Oncoimmunology · 2025Article
- Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.Discover oncology · 2025Review
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.Cancer research communications · 2025Article
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Perils and Problems in Bispecific T-Cell Engager Antibodies.Current drug safety · 2025Review
- Roles of immunosuppressive myeloid states in colorectal cancer checkpoint inhibitor non-response: single-cell and spatial proteomics, and reprogramming approaches.Frontiers in immunology · 2025Review
- Hypoxic link between cancer cells and the immune system: The role of adenosine and lactate.Oncology research · 2025Review
- Review
- Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism.Cell communication and signaling : CCS · 2024Review
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy.Cell death & disease · 2024Review
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- Recent advances in immunotherapy and its combination therapies for advanced melanoma: a review.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCluster of differentiation (CD)73-adenosine and transforming growth factor (TGF)-β pathways are involved in abrogated antitumor immune responses and can lead to protumor conditions. This Phase 1 study (NCT03954704) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of dalutrafusp alfa (also known as GS-1423 and AGEN1423), a bifunctional, humanized, aglycosylated immunoglobulin G1 kappa antibody that selectively inhibits CD73-adenosine production and neutralizes active TGF-β signaling in patients with advanced solid tumors.
methodsDose escalation started with an accelerated titration followed by a 3+3 design. Patients received dalutrafusp alfa (0.3, 1, 3, 10, 20, 30, or 45 mg/kg) intravenously every 2 weeks (Q2W) up to 1 year or until progressive disease (PD) or unacceptable toxicity.
resultsIn total, 21/22 patients received at least one dose of dalutrafusp alfa. The median number of dalutrafusp alfa doses administered was 3 (range 1-14). All patients had at least one adverse event (AE), most commonly fatigue (47.6%), nausea (33.3%), diarrhea (28.6%), and vomiting (28.6%). Nine (42.9%) patients had a Grade 3 or 4 AE; two had Grade 5 AEs of pulmonary embolism and PD, both unrelated to dalutrafusp alfa. Target-mediated drug disposition appears to be saturated at dalutrafusp alfa doses above 20 mg/kg. Complete CD73 target occupancy on B cells and CD8+ T cells was observed, and TGF-β 1/2/3 levels were undetectable at dalutrafusp alfa doses of 20 mg/kg and higher. Free soluble (s)CD73 levels and sCD73 activity increased with dalutrafusp alfa treatment. Seventeen patients reached the first response assessment, with complete response, partial response, stable disease, and PD in 0, 1 (4.8%), 7 (33.3%), and 9 (42.9%) patients, respectively.
conclusionsDalutrafusp alfa doses up to 45 mg/kg Q2W were well tolerated in patients with advanced solid tumors. Additional evaluation of dalutrafusp alfa could further elucidate the clinical utility of targeting CD73-adenosine and TGF-β pathways in oncology.
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