dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Voss, Martin H. |
dc.contributor.author | Gordon, Michael S. |
dc.contributor.author | Mita, Monica |
dc.contributor.author | Rini, Brian |
dc.contributor.author | Macarulla Mercadé, Teresa |
dc.contributor.author | Makker, Vicky |
dc.date.accessioned | 2021-11-05T06:58:39Z |
dc.date.available | 2021-11-05T06:58:39Z |
dc.date.issued | 2020-11 |
dc.identifier.citation | Voss MH, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, et al. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer. 2020 Nov;123:1590–8. |
dc.identifier.issn | 1532-1827 |
dc.identifier.uri | https://hdl.handle.net/11351/6503 |
dc.description | Cancer therapy; Gynaecological cancer; Urological cancer |
dc.description.abstract | Background
This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours.
Methods
Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients).
Results
Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers.
Conclusions
Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer. |
dc.language.iso | eng |
dc.publisher | Springer Nature |
dc.relation.ispartofseries | British Journal of Cancer;123 |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Càncer - Tractament |
dc.subject | Medicaments - Administració |
dc.subject.mesh | Neoplasms |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Maximum Tolerated Dose |
dc.title | Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1038/s41416-020-01041-x |
dc.subject.decs | neoplasias |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | dosis máxima tolerada |
dc.relation.publishversion | https://doi.org/10.1038/s41416-020-01041-x |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Voss MH, Makker V] Department of Medicine, 300 East 66th Street, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Gordon MS] Oncology Research, HonorHealth Research Institute, 10510 N 92nd St Suite 200, Scottsdale, AZ 85258, USA. [Mita M] Department of Hematology and Oncology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd North Tower, Los Angeles, CA 90048, USA. [Rini B] Cleveland Clinic Foundation, Department of Solid Tumor Oncology, 9500 Euclid Avenue, Cleveland, OH 44195, USA. [Macarulla T] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain |
dc.identifier.pmid | 32913286 |
dc.identifier.wos | 000568843200001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |