ArticleBritish journal of cancer2020
Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02039336 (Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer), which is not on this map. Cited by 33 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.
Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer
Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Safety and efficacy of lapatinib, binimetinib, and vinorelbine for RAS mutant metastatic colorectal cancer: results of the RASTRIC Phase I/II trial.British journal of cancer · 2026Trial
- Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.Targeted oncology · 2026Review
- Network toxicology and bioinformatics reveal potential molecular links between cadmium exposure and pancreatic cancer.BMC pharmacology & toxicology · 2026Article
- Efficacy of dual KRASCell death & disease · 2026Article
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Review
- A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.BJC reports · 2025Article
- Article
- Development and validation of a novel signature to predict the survival and affect the immune microenvironment of esophageal squamous cell carcinoma: epigenetic-related genes.Frontiers in immunology · 2025Article
- Pan-Cancer Analysis of Enhancer-Induced PAN3-AS1 and Experimental Validation as a WFDC13-Promoting Factor in Colon Cancer.Oncology research · 2025Article
- Article
- Novel biomarkers and drug correlations of non-canonical WNT signaling in prostate and breast cancer.Discover oncology · 2024Article
- Identifying drug candidates for pancreatic ductal adenocarcinoma based on integrative multiomics analysis.Journal of gastrointestinal oncology · 2024Article
- Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer.Current treatment options in oncology · 2023Review
- A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in KRAS result in a constitutively activated MAPK pathway. In KRAS-mutant tumours existing treatment options, e.g. MEK inhibition, have limited efficacy due to resistance through feedback activation of epidermal growth factor receptors (HER).
methodsIn this Phase 1 study, the pan-HER inhibitor dacomitinib was combined with the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutant colorectal, pancreatic and non-small-cell lung cancer (NSCLC). Patients received escalating oral doses of once daily dacomitinib and twice daily PD-0325901 to determine the recommended Phase 2 dose (RP2D). (Clinicaltrials.gov: NCT02039336).
resultsEight out of 41 evaluable patients (27 colorectal cancer, 11 NSCLC and 3 pancreatic cancer) among 8 dose levels experienced dose-limiting toxicities. The RP2D with continuous dacomitinib dosing was 15 mg of dacomitinib plus 6 mg of PD-0325901 (21 days on/7 days off), but major toxicity, including rash (85%), diarrhoea (88%) and nausea (63%), precluded long-term treatment. Therefore, other intermittent schedules were explored, which only slightly improved toxicity. Tumour regression was seen in eight patients with the longest treatment duration (median 102 days) in NSCLC.
conclusionsAlthough preliminary signs of antitumour activity in NSCLC were seen, we do not recommend further exploration of this combination in KRAS-mutant patients due to its negative safety profile.
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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.