ArticleTargeted oncology2020
Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer.
Article in Targeted oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01392521 (Phase Ib Trial of the Combination of PI3K Inhibitor BAY 80-6946 and Allosteric-MEK Inhibitor BAY 86-9766 in Subjects With Advanced Cancer), which is not on this map. Cited by 33 papers.
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.
Phase Ib Trial of the Combination of PI3K Inhibitor BAY 80-6946 and Allosteric-MEK Inhibitor BAY 86-9766 in Subjects With Advanced Cancer
Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Phase II Trial of Vemurafenib and Sorafenib Combination in AdvancedJournal of immunotherapy and precision oncology · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Targeting KRAS in colorectal cancer (Review).Molecular and clinical oncology · 2025Review
- Review
- Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models.British journal of cancer · 2025Article
- Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel inTherapeutic advances in medical oncology · 2024Article
- Suppression of Tumor Cell Lactate-generating Signaling Pathways Eradicates Murine PTEN/p53-deficient Aggressive-variant Prostate Cancer via Macrophage Phagocytosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives.RSC medicinal chemistry · 2023Review
- Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non-Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042).Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer.Molecular cancer therapeutics · 2023Article
- Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis.bioRxiv : the preprint server for biology · 2023Article
- The Therapeutic Landscape forCancers · 2023Review
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Phosphoinositide 3-Kinase (PI3K) Inhibitors and Breast Cancer: An Overview of Current Achievements.Cancers · 2023Review
- Combining MEK and SRC inhibitors for treatment of colorectal cancer demonstrate increased efficacy in vitro but not in vivo.PloS one · 2023Article
- KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.The oncologist · 2022Article
- Review
- Integrated analysis of pivotal biomarker of LSM1, immune cell infiltration and therapeutic drugs in breast cancer.Journal of cellular and molecular medicine · 2022Article
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDual inhibition of PI3K and MAPK signaling is conceptually a promising anticancer therapy.
objectiveThis phase 1b trial investigated the safety, maximum tolerated dose (MTD), recommended phase II dose, pharmacokinetics, tumor response, fluorodeoxyglucose positron emission tomography (FDG-PET) pharmacodynamics, and biomarker explorations for the combination of pan-PI3K inhibitor copanlisib and allosteric MEK inhibitor refametinib in patients with advanced solid tumors. PATIENTS AND
methodsThis was an adaptive trial with eight dose cohorts combining dose escalation and varying schedules in repeated 28-day cycles. Patients received copanlisib (0.2-0.8 mg/kg intravenously) intermittently (days 1, 8, 15) or weekly (days 1, 8, 15, 22) each cycle, and refametinib (30-50 mg twice daily orally) continuously or 4 days on/3 days off. Patients with KRAS, NRAS, BRAF, or PI3KCA mutations were eligible for the expansion cohort.
resultsIn the dose-escalation (n = 49) and expansion (n = 15) cohorts, the most common treatment-emergent adverse events included diarrhea (59.4%), nausea, acneiform rash, and fatigue (51.6% each). Dose-limiting toxicities included oral mucositis (n = 4), increased alanine aminotransferase/aspartate aminotransferase (n = 3), rash acneiform, hypertension (n = 2 each), and diarrhea (n = 1). MTD was copanlisib 0.4 mg/kg weekly and refametinib 30 mg twice daily. No pharmacokinetic interactions were identified. Decreased tumor FDG uptake and MEK-ERK signaling inhibition were demonstrated during treatment. Best response was stable disease (n = 21); median treatment duration was 6 weeks.
conclusionsDespite sound rationale and demonstrable pharmacodynamic tumor activity in relevant tumor populations, a dose and schedule could not be identified for this drug combination that was both tolerable and offered clear efficacy in the population assessed. CLINICALTRIALS. GOV IDENTIFIER: NCT01392521.
Identifiers
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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.