ArticleThe oncologist2023
A Phase Ib/II Study of WNT974 + Encorafenib + Cetuximab in Patients With BRAF V600E-Mutant KRAS Wild-Type Metastatic Colorectal Cancer.
Article in The oncologist, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02278133 (A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations), which is not on this map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
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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.
A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Targeted therapy in advancedBMJ (Clinical research ed.) · 2025Pooled it
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
- Review
- Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Tumor-targeted bispecific antibodies effectively inhibit oncogenic pathways while minimizing toxicity.Science advances · 2026Article
- Functional roles and clinical potential of SOX1 in cancer as a biomarker and therapeutic target.Discover oncology · 2026Review
- Chemotherapy-Treated Breast Cancer Cells Activate the WNT Signaling Pathway to Enter a Diapause-Like Early Persister State.Cancer research · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Oncofetal reprogramming and cellular plasticity in colorectal cancer: from mechanisms to clinical translation.Frontiers in oncology · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Exploring the Roles of Wnt Signaling Pathway and Non-Coding RNAs in COPD.International journal of chronic obstructive pulmonary disease · 2026Review
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Wnt5a-mediated Adipo-Cardiac Interorgan Communication in HFpEF.bioRxiv : the preprint server for biology · 2025Article
- Dual role of WNT10A in promoting the malignancy of glioblastoma and remodeling the tumor microenvironment.Neuro-oncology · 2025Article
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- The β-1,4 GalT-V Interactome-Potential Therapeutic Targets and a Network of Pathways Driving Cancer and Cardiovascular and Inflammatory Diseases.International journal of molecular sciences · 2025Review
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- The co-receptor Tetraspanin12 directly captures Norrin to promote ligand-specific β-catenin signaling.eLife · 2025Article
- Genomic alterations in the WNT/β-catenin pathway and resistance of colorectal cancer cells to pathway-targeting therapies.Exploration of targeted anti-tumor therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 10 institutions in 7 countries.
Funding
Abstract
backgroundWNT974 is a small molecule inhibitor of Wnt signaling that specifically inhibits porcupine O-acyltransferase. This phase Ib dose--escalation study evaluated the maximum tolerated dose of WNT974 in combination with encorafenib and cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer with RNF43 mutations or RSPO fusions. PATIENTS AND
methodsPatients received once-daily encorafenib and weekly cetuximab, in addition to once-daily WNT974, in sequential dosing cohorts. In the first cohort, patients received 10-mg WNT974 (COMBO10), which was reduced in subsequent cohorts to 7.5-mg (COMBO7.5) or 5-mg (COMBO5) after dose-limiting toxicities (DLTs) were observed. Primary endpoints were incidence of DLTs and exposure to WNT974 and encorafenib. Secondary endpoints were anti-tumor activity and safety.
resultsTwenty patients were enrolled (COMBO10, n = 4; COMBO7.5, n = 6; COMBO5, n = 10). DLTs were observed in 4 patients, including grade 3 hypercalcemia (COMBO10, n = 1; COMBO7.5, n = 1), grade 2 dysgeusia (COMBO10, n = 1), and lipase increased (COMBO10, n = 1). A high incidence of bone toxicities (n = 9) was reported, including rib fracture, spinal compression fracture, pathological fracture, foot fracture, hip fracture, and lumbar vertebral fracture. Serious adverse events were reported in 15 patients, most frequently bone fracture, hypercalcemia, and pleural effusion. The overall response rate was 10% and disease control rate 85%; most patients achieved stable disease as their best response.
conclusionConcerns surrounding the safety and lack of preliminary evidence of improved anti-tumor activity of WNT974 + encorafenib + cetuximab, compared with previous encorafenib + cetuximab data, ultimately led to study discontinuation. Phase II was not initiated.
trial registrationClinicalTrials.gov, NCT02278133.
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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.