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NCT03266159

A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity of GSK525762 Plus Trametinib in Subjects With Solid Tumors

Withdrawn Phase 2 Last updated 8 December 2017
What this trial tests

Phase 2 trial testing GSK525762 Besylate tablets in Solid Tumours. Withdrawn.

Timeline
27 November 2017
Primary endpoint
19 August 2020
19 August 2020

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusWithdrawn
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Start date27 November 2017
Primary completion19 August 2020
Estimated completion19 August 2020

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Solid Tumours. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

GSK525762 is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Trametinib is a potent inhibitor of the mitogen-activated protein kinase proteins (MEK1 and MEK2). GSK525762 and trametinib are critical for growth and survival of tumor cells. This will be the first study demonstrating the synergistic effect of BET inhibitor and MEK inhibitor administered together against tumor cell growth. This study aims to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of combination of GSK525762 and trametinib when administered concomitantly to subjects with small cell lung cancer (SCLC) and rat sarcoma virus oncogene homolog (Ras) mutated solid tumors. The study will be conducted in two parts; part 1 will consists of dose escalation and dose expansion cohorts and part 2 will consists of four disease specific cohorts (SCLC, Ras-mutated adenocarcinoma \[RMAC\] of the colon \[Ras-mutated colorectal cancer {RMCRC}\] and/or rectum, Ras-mutated non small cell lung cancer \[RMNSCLC\], Ras-mutated pancreatic adenocarcinoma \[RMPAC\]) and an optional "basket" cohort (Ras-pathway activated solid tumors \[RAST\]). Part 1 will focus on selection of the Part 2 dose based on safety/tolerability, PK, PD, and efficacy. Part 2 will investigate the overall response rate and clinical response. The total duration of study will be approximately three years (nine to twelve months for part 1 and two years for part 2). Approximately 138-156 subjects will be enrolled in the study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting oncogenic Myc as a strategy for cancer treatment.
    Chen H, Liu H, Qing G. · · 2018 · cited 595× · PMID 29527331 · DOI 10.1038/s41392-018-0008-7
  2. Achieving clinical success with BET inhibitors as anti-cancer agents.
    Shorstova T, Foulkes WD, Witcher M. · · 2021 · cited 272× · PMID 33723398 · DOI 10.1038/s41416-021-01321-0
  3. Epigenetics-targeted drugs: current paradigms and future challenges.
    Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
  4. Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.
    Wang ZQ, Zhang ZC, Wu YY, Pi YN, et al · · 2023 · cited 128× · PMID 37926722 · DOI 10.1038/s41392-023-01647-6
  5. Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.
    Tang P, Zhang J, Liu J, Chiang CM, et al · · 2021 · cited 109× · PMID 33616410 · DOI 10.1021/acs.jmedchem.0c01487
  6. Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.
    Manzotti G, Ciarrocchi A, Sancisi V. · · 2019 · cited 60× · PMID 30841549 · DOI 10.3390/cancers11030304
  7. BET Proteins as Attractive Targets for Cancer Therapeutics.
    Sarnik J, Popławski T, Tokarz P. · · 2021 · cited 51× · PMID 34681760 · DOI 10.3390/ijms222011102
  8. Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.
    Frattaruolo L, Brindisi M, Curcio R, Marra F, et al · · 2020 · cited 50× · PMID 32825551 · DOI 10.3390/ijms21176014

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Other recruiting trials for Solid Tumours

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