Evidence map›Paper›PMID 38411735›Full record

ArticleCancer chemotherapy and pharmacology2024

A first-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors.

Toshihiko Doi, Shunji Takahashi, Daisuke Aoki, Kan Yonemori, Hiroki Hara, Kosei Hasegawa, Kazuhiro Takehara, Kenichi Harano, Mayu Yunokawa, Hiroyuki Nomura and 4 more

Open access · hybridAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 8 institutions in 1 country.

Toshihiko DoiNational Cancer Center Hospital East, Kashiwa, Japan. tdoi@east.ncc.go.jp.ORCID 0000-0003-2042-6829
Shunji TakahashiCancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Daisuke AokiKeio University School of Medicine, Tokyo, Japan.
Kan YonemoriNational Cancer Center Hospital, Tokyo, Japan.
Hiroki HaraSaitama Cancer Center, Kita-Adachi, Japan.
Kosei HasegawaSaitama Medical University International Medical Center, Hidaka, Japan.
Kazuhiro TakeharaNHO Shikoku Cancer Center, Matsuyama, Japan.
Kenichi HaranoNational Cancer Center Hospital East, Kashiwa, Japan.
Mayu YunokawaCancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Hiroyuki NomuraKeio University School of Medicine, Tokyo, Japan.
Tatsunori ShimoiNational Cancer Center Hospital, Tokyo, Japan.
Koji HorieSaitama Cancer Center, Kita-Adachi, Japan.
Aiko OgasawaraSaitama Medical University International Medical Center, Hidaka, Japan.
Shinichi OkameNHO Shikoku Cancer Center, Matsuyama, Japan.
Japanese Foundation For Cancer Research · JPNational Cancer Center Hospital East · JPSaitama Cancer Center · JPSaitama Medical University · JPShikoku Cancer Center · JPTokyo National Hospital · JPFujita Health University · JPKeio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTAS-117 is a highly potent and selective, oral, allosteric pan-AKT inhibitor under development for advanced/metastatic solid tumors. The safety, clinical pharmacology, pharmacogenomics and efficacy were investigated.

methodsThis phase I, open-label, non-randomized, dose-escalating, first-in-human study enrolled patients with advanced/metastatic solid tumors and comprised three phases (dose escalation phase [DEP], regimen modification phase [RMP], and safety assessment phase [SAP]). The SAP dose and regimen were determined in the DEP and RMP. Once-daily and intermittent dosing (4 days on/3 days off, 21-day cycles) were investigated. The primary endpoints were dose-limiting toxicities (DLTs) in Cycle 1 of the DEP and RMP and incidences of adverse events (AEs) and adverse drug reactions (ADRs) in the SAP. Secondary endpoints included pharmacokinetics, pharmacodynamics, pharmacogenomics, and antitumor activity.

resultsOf 66 enrolled patients, 65 received TAS-117 (DEP, n = 12; RMP, n = 10; SAP, n = 43). No DLTs were reported with 24-mg/day intermittent dosing, which was selected as a recommended dose in SAP. In the SAP, 98.5% of patients experienced both AEs and ADRs (grade ≥ 3, 67.7% and 60.0%, respectively). In the dose range tested (8 to 32 mg/day), TAS-117 pharmacokinetics were dose proportional, and pharmacodynamic analysis showed a reduction of phosphorylated PRAS40, a direct substrate of AKT. Four patients in the SAP had confirmed partial response.

conclusionOral doses of TAS-117 once daily up to 16 mg/day and intermittent dosing of 24 mg/day were well tolerated. TAS-117 pharmacokinetics were dose proportional at the doses evaluated. Antitumor activity may occur through AKT inhibition.

trial registrationjRCT2080222728 (January 29, 2015).

Indexed as

Dose-Response Relationship, DrugNeoplasmsProto-Oncogene Proteins c-aktAdultAgedAged, 80 and overAllosteric RegulationAntineoplastic AgentsFemaleHumansMaleMaximum Tolerated DoseMiddle AgedProtein Kinase InhibitorsPyrazolesThiophenesafuresertibAntineoplastic AgentsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyrazolesThiophenesAdvanced solid tumorAKT inhibitorFirst-in-humanPharmacodynamicsPharmacokinetics

Identifiers

PMID38411735
PMCPMC11129975
OpenAlexW4392193105

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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 Socratic graph.