ArticleESMO open2018
Phase I study of the investigational oral mTORC1/2 inhibitor sapanisertib (TAK-228): tolerability and food effects of a milled formulation in patients with advanced solid tumours.
Article in ESMO open, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02412722 (A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MLN0128), which is not on this map. Cited by 25 papers.
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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 1, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MLN0128 (an Oral mTORC 1/2 Inhibitor) as a Single Agent and in Combination With Paclitaxel in Adult Patients With Advanced Nonhematologic Malignancies
Who cites it
25 citing papers in PubMed.
- A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer.Gynecologic oncology · 2023Trial
- Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy.The oncologist · 2022Trial
- Sapanisertib plus Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive/HER2-Negative Advanced Breast Cancer after Progression on Aromatase Inhibitor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- ANETT: PhAse II trial of NEoadjuvant TAK-228 plus Tamoxifen in patients with hormone receptor-positive breast cancer.Breast cancer research and treatment · 2021Trial
- mTOR inhibition enhances the antitumor efficacy of pan-RAF-MEK blockade by inhibiting the ATF4-MTHFD2 pathway.Cell death & disease · 2026Article
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Targeting NFE2L2/KEAP1 Mutations in Advanced NSCLC With the TORC1/2 Inhibitor TAK-228.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- Dual mTORC1/2 inhibition compromises cell defenses against exogenous stress potentiating Obatoclax-induced cytotoxicity in atypical teratoid/rhabdoid tumors.Cell death & disease · 2022Article
- Ponatinib, Lestaurtinib, and mTOR/PI3K Inhibitors Are Promising Repurposing Candidates against Entamoeba histolytica.Antimicrobial agents and chemotherapy · 2022Article
- A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies.Targeted oncology · 2022Article
- Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition.Scientific reports · 2021Article
- Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors.Cancers · 2021Article
- TORC1/2 kinase inhibition depletes glutathione and synergizes with carboplatin to suppress the growth of MYC-driven medulloblastoma.Cancer letters · 2021Article
- Establishment and characterisation of testicular cancer patient-derived xenograft models for preclinical evaluation of novel therapeutic strategies.Scientific reports · 2020Article
- Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1/2 Inhibition in a Preclinical Model of Mucosal Melanoma.Molecular cancer therapeutics · 2020Article
- Phase 1 Study to Evaluate the Effect of the Investigational Anticancer Agent Sapanisertib on the QTc Interval in Patients With Advanced Solid Tumors.Clinical pharmacology in drug development · 2020Article
- Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-RSC medicinal chemistry · 2020Review
- Synergistic activity of mTORC1/2 kinase and MEK inhibitors suppresses pediatric low-grade glioma tumorigenicity and vascularity.Neuro-oncology · 2020Article
- Efficacy of FGFR Inhibitors and Combination Therapies for Acquired Resistance in FGFR2-Fusion Cholangiocarcinoma.Molecular cancer therapeutics · 2020Article
- mTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs).Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSapanisertib (TAK-228) is an investigational, orally available, potent and highly selective mTORC1/2 inhibitor demonstrating promise in numerous malignancies. This phase I study (NCT02412722) evaluated the safety, tolerability, pharmacokinetics and antitumour activity of single-agent TAK-228 (milled capsules), administered daily (QD) or weekly (QW) and in combination with paclitaxel in patients with advanced solid tumours. Pharmacokinetic comparisons of milled versus unmilled TAK-228 and the impact of food were also investigated.
methodsPatients were enrolled to receive: TAK-228 QD, TAK-228 3 days/week plus paclitaxel 80 mg/m
resultsSixty-one adults were enrolled. Maximum tolerated doses for milled TAK-228 were 3 mg (TAK-228 QD), 6 mg (TAK-228+P) and 30 mg (TAK-228 QW). Most patients reported ≥1 adverse event (AE); there were no meaningful differences in drug-related AEs across regimens or doses. Three on-study deaths occurred, all considered unrelated to study drugs. TAK-228 pharmacokinetics did not differ between unmilled/milled capsules or with/without paclitaxel. However, TAK-228 C
conclusionsMilled TAK-228 was well tolerated with signs of antitumour activity; administration did not reduce overall exposure (area under the plasma concentration-time curve) but reduced C TRIAL REGISTRATION NUMBER: NCT02412722.
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