Evidence map›Paper›PMID 34843044›Full record

ArticleTargeted oncology2022

A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies.

Toshio Shimizu, Yasutoshi Kuboki, Chia-Chi Lin, Kan Yonemori, Tomoko Yanai, Douglas V Faller, Lwona Dobler, Neeraj Gupta, Farhad Sedarati, Kyu-Pyo Kim

Erratum issued Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Targeted oncology, 2022. 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 NCT03370302 (A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-228), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 35% 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.

NCT03370302 phase1terminatednot on this map

A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-228 (a Catalytic TORC1/2 Inhibitor) as Single Agent in Adult East Asian Patients With Advanced Nonhematological Malignancies

TypeinterventionalSponsorCalithera Biosciences, IncRan2018 to 2019Enrolled28ConditionsAdvanced Nonhematological NeoplasmsArmsTAK-228
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 4 countries.

Toshio ShimizuDepartment of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. tosshimi@ncc.go.jp.ORCID 0000-0001-6632-0638
Yasutoshi KubokiNational Cancer Center Hospital East, Chiba, Japan.ORCID 0000-0003-3675-953X
Chia-Chi LinNational Taiwan University Hospital, Taipei, Taiwan.ORCID 0000-0002-2573-5789
Kan YonemoriDepartment of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.ORCID 0000-0002-7624-7611
Tomoko YanaiTakeda Pharmaceutical Company Limited, Osaka, Japan.ORCID 0000-0002-2753-5078
Douglas V FallerMillennium Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.ORCID 0000-0002-2454-3478
Lwona DoblerMillennium Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.ORCID 0000-0001-5911-852X
Neeraj GuptaMillennium Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.ORCID 0000-0002-5500-5218
Farhad SedaratiMillennium Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
Kyu-Pyo KimAsan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.ORCID 0000-0001-7848-5923
Takeda (United States) · USNational Cancer Center · USNational Cancer Center Hospital East · JPNational Taiwan University Hospital · TWTakeda (Japan) · JPTokyo National Hospital · JPUlsan College · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSapanisertib is an oral, highly selective inhibitor of mammalian target of rapamycin complexes 1 and 2.

objectiveThe aim of this study was to assess the safety, tolerability, pharmacokinetics, preliminary efficacy, and to establish the recommended phase 2 dose (RP2D) of sapanisertib. PATIENTS AND

methodsIn this dose-escalation and expansion study, East Asian patients with nonhematologic malignancies received increasing sapanisertib doses once-daily (QD; starting at 2 mg) or once-weekly (QW; starting at 20 mg) in 28-day cycles.

resultsAmong 28 patients (QD dosing, n = 22; QW dosing, n = 6), three dose-limiting toxicities were reported (stomatitis [n = 2], gastrointestinal inflammation, gingivitis, and acute myocardial infarction [all n = 1]), all in the 4 mg QD cohort. The RP2D of sapanisertib was 3 mg QD. The most common adverse events were stomatitis (64%), nausea (50%), and decreased appetite (50%) in the QD arm, and nausea (100%), blood alkaline phosphatase increased (67%), and hyperglycemia (67%) in the QW arm. The T

conclusionsThe RP2D of sapanisertib in East Asian patients (3 mg QD) was lower than in Western patients (4 mg QD), but the pharmacokinetics and safety profiles were similar. Sapanisertib was well tolerated and showed moderate anti-tumor effects in heavily pretreated patients with nonhematologic malignancies. NCT NUMBER: NCT03370302; Registered December 7, 2017.

Indexed as

Antineoplastic AgentsNeoplasmsStomatitisAdenineBenzoxazolesDose-Response Relationship, DrugHumansMaximum Tolerated DoseNauseaPyrazolesPyrimidinesAdenineAntineoplastic AgentsBenzoxazolesPyrazolesPyrimidinessapanisertib

Identifiers

PMID34843044
PMCPMC8994735
OpenAlexW3216067455

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.