Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2025
Results of the Phase I/II Study and Preliminary B-cell Gene Signature of Combined Inhibition of Glutamine Metabolism and EGFR in Colorectal Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- The Next Frontier in Quantitative Co-Clinical Imaging to Advance Functional Precision Oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances.International journal of molecular sciences · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Integrated analysis of glutamine metabolism and immune microenvironment identifies GOT2 as a prognostic gene in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Metabolic reprogramming as a key regulator in Helicobacter pylori-infected gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Review
- Review
- Therapeutic Potential of Glutaminase Inhibition Targeting Metabolic Adaptations in Resistant Melanomas to Targeted Therapy.International journal of molecular sciences · 2025Article
- Glutamine metabolism remodels tumor-associated macrophage: mechanistic explorations and new strategies in translational medicine.Frontiers in immunology · 2025Review
- Immune suppression in MTAP-deficient cancers via glutamate metabolism and CXCL10 downregulation.Frontiers in immunology · 2025Article
- Targeting emerging amino acid dependencies and transporters in cancer therapy.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
purposeEGFR-targeting mAbs are essential for managing rat sarcoma virus wild-type metastatic colorectal cancer (mCRC), but their limited efficacy necessitates exploring immunologic and metabolic factors influencing response. This study evaluated glutamine metabolism targeting with EGFR inhibition to identify response biomarkers in patients with prior anti-EGFR treatment progression. PATIENTS AND
methodsWe conducted a phase I/II trial in patients with KRAS wild-type mCRC, combining panitumumab (6 mg/kg) and CB-839 (600 mg/kg or 800 mg/kg), hypothesizing that the dual inhibition of glutamine metabolism and MAPK signaling would enhance outcomes. As study correlatives, we investigated the B-cell activation signature "B-score" and glutamine PET as potential treatment response biomarkers.
resultsThe combination of panitumumab and CB-839 was tolerable with manageable side effects, including grade 4 hypomagnesemia in four patients, a known panitumumab-related event. Two patients achieved partial response, and five had stable disease, with a 41% disease control rate. Median progression-free survival and overall survival were 1.84 and 8.87 months, respectively. A positive correlation between "B-score" and lesion size reduction suggested its association with clinical benefit (partial response and stable disease). Lower "B-score" correlated with greater tumor avidity for glutamine by PET, indicating B-cell activation sensitivity to glutamine depletion.
conclusionsThe combination of CB-839 and panitumumab showed safety and promising preliminary responses, but the study closed early due to CB-839 development termination. The B-cell activation signature "B-score" emerged as a potential biomarker for EGFR and glutaminase inhibition in mCRC, warranting further studies. These findings suggest opportunities to improve immune response and therapies in glutaminolysis-dependent tumors.
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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.