Trial reportGynecologic oncology2019
Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study.
Trial report in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04486352 (A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer), which is not on this map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer
Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2025Trial
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Evaluation of the contribution of randomised cancer clinical trials evaluating agents without documented single-agent activity.ESMO open · 2020Trial
- Review
- Dual FAK and EPHA2 targeting by brigatinib tackles PARP inhibitor adaptive survival response in high-grade serous ovarian cancer.Science translational medicine · 2026Article
- A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).BMC cancer · 2025Article
- High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Integrated Identification and Immunotherapy Response Analysis of the Prognostic Signature Associated With m6A, Cuproptosis-Related, Ferroptosis-Related lncRNA in Endometrial Cancer.Cancer reports (Hoboken, N.J.) · 2024Article
- Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.Cells · 2024Review
- Novel Molecular Targets in Endometrial Cancer: Mechanisms and Perspectives for Therapy.Biologics : targets & therapy · 2024Review
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Article
- BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer.Cancers · 2023Article
- Targeting the PI3K Pathway in Gynecologic Malignancies.Current oncology reports · 2022Review
- Antitumorigenic effect of combination treatment with ONC201 and TRAIL in endometrial cancerCancer biology & therapy · 2021Article
- Next-Generation Sequencing in the Diagnosis of Metastatic Lesions: Reclassification of a Glioblastoma as an Endometrial Cancer Metastasis to the Brain.The oncologist · 2021Article
- AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B.Cancer discovery · 2021Article
- OncogenicCancers · 2021Review
- New strategies for targeting kinase networks in cancer.The Journal of biological chemistry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 12 institutions in 1 country.
Funding
Abstract
objectiveWe sought to determine safety and efficacy of the AKT inhibitor, GSK2141795, combined with the MEK inhibitor, trametinib, in endometrial cancer.
methodsPatients with measurable recurrent endometrial cancer were eligible. One to two prior cytotoxic regimens were allowed; prior use of a MEK or PI3K pathway inhibitor was excluded. Initial trial design consisted of a KRAS mutation stratified randomized phase II with a safety lead-in evaluating the combination. For the safety lead in, the previously recommended phase 2 dose (RP2D; trametinib 1.5 mg, GSK2141795 50 mg) was chosen for Dose Level 1 (DL1).
resultsOf 26 enrolled patients, 14 were treated on DL1 and 12 were treated on DL-1 (trametinib 1.5 mg, GSK2141795 25 mg). Most common histologies were endometrioid (58%) and serous (27%). Four of 25 (16%) patients were KRAS mutant. Dose limiting toxicities (DLTs) were assessed during cycle 1. DL1 had 8 DLTs (hypertension (n = 2), mucositis (2), rash (2), dehydration, stroke/acute kidney injury). DL1 was deemed non-tolerable so DL-1 was explored. DL-1 had no DLTs. Sixty-five percent of patients had ≥ grade 3 toxicity. There were no responses in DL1 (0%, 90%CI 0-15%) and 1 response in DL-1 (8.3%, 90%CI 0.4-33.9%). Proportion PFS at 6 months for DL1 is 14%, and 25% for DL-1.
conclusionThe combination of trametinib and GSK2141795 had high levels of toxicity in endometrial cancer at the previously RP2D but was tolerable at a reduced dose. Due to insufficient preliminary efficacy at a tolerable dose, the Phase II study was not initiated.
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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.