TAKTIC: A prospective, multicentre, uncontrolled, phase IB/II study of LY2780301, a p70S6K/AKT inhibitor, in combination with weekly paclitaxel in HER2-negative advanced breast cancer patients.

Adult Aged Antineoplastic Combined Chemotherapy Protocols / therapeutic use Enzyme Inhibitors / administration & dosage Female Humans Middle Aged Paclitaxel / administration & dosage Proto-Oncogene Proteins c-akt / antagonists & inhibitors Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors Triple Negative Breast Neoplasms / drug therapy

AKT Metastatic breast cancer PI3K Paclitaxel

Journal

European journal of cancer (Oxford, England : 1990)

ISSN: 1879-0852

Titre abrégé: Eur J Cancer

Pays: England

ID NLM: 9005373

Informations de publication

Date de publication:
12 2021

Historique:

received: 14 06 2021

revised: 22 09 2021

accepted: 25 09 2021

pubmed: 16 11 2021

medline: 17 12 2021

entrez: 15 11 2021

Statut: ppublish

Résumé

Hormone-resistant HER2-negative or triple-negative advanced breast cancers (ABC) are routinely treated with paclitaxel chemotherapy. LY2780301 is a dual inhibitor of p70 ribosomal protein S6 kinase and AKT. The TAKTIC study aimed at exploring the combination of paclitaxel and LY2780301 in this population. In this multicentric phase Ib/II trial, we enrolled patients with HER2-negative ABC, with (phase IB) or without (phase II) prior to cytotoxic treatment for advanced disease. Oral LY2780301 was administered once daily in combination with intravenous weekly paclitaxel. Primary endpoints were to determine the recommended phase II dose (RP2D) of the combination of LY2780301 with weekly paclitaxel (phase Ib), and to estimate a 6 months objective response rate (ORR) (phase II) in patients with HER2-negative ABC, both in the overall patient population and in cases with activation of the PI3K/AKT pathway (PI3KAKT+). A total of 51 patients were enrolled; RP2D was LY2780301 500 mg QD+ paclitaxel 80 mg/m Combining LY2780301 and weekly paclitaxel in patients with HER2-negative ABC was feasible with preliminary evidence of efficacy in both the overall population and the PI3KAKT+ subgroup. NCT01980277.

Sections du résumé

BACKGROUND

METHODS

In this multicentric phase Ib/II trial, we enrolled patients with HER2-negative ABC, with (phase IB) or without (phase II) prior to cytotoxic treatment for advanced disease. Oral LY2780301 was administered once daily in combination with intravenous weekly paclitaxel. Primary endpoints were to determine the recommended phase II dose (RP2D) of the combination of LY2780301 with weekly paclitaxel (phase Ib), and to estimate a 6 months objective response rate (ORR) (phase II) in patients with HER2-negative ABC, both in the overall patient population and in cases with activation of the PI3K/AKT pathway (PI3KAKT+).

RESULTS

A total of 51 patients were enrolled; RP2D was LY2780301 500 mg QD+ paclitaxel 80 mg/m

CONCLUSION

Combining LY2780301 and weekly paclitaxel in patients with HER2-negative ABC was feasible with preliminary evidence of efficacy in both the overall population and the PI3KAKT+ subgroup.

TRIAL REGISTRATION ID

NCT01980277.

Identifiants

DOI: 10.1016/j.ejca.2021.09.040 PMID: 34781168

pubmed: 34781168

pii: S0959-8049(21)01141-2

doi: 10.1016/j.ejca.2021.09.040

pii:

doi:

Substances chimiques

Enzyme Inhibitors 0

Proto-Oncogene Proteins c-akt EC 2.7.11.1

Ribosomal Protein S6 Kinases, 70-kDa EC 2.7.11.1

Paclitaxel P88XT4IS4D

Banques de données

ClinicalTrials.gov

['NCT01980277']

Types de publication

Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

205-214

Informations de copyright

Déclaration de conflit d'intérêts

Conflict of interest statement CV received research a grant from BMS, participated in the advisory board for Pfizer and Novartis. AG received non-financial support from Roche, Novartis, AstraZeneca and Pfizer. RS received research grants from EISAI and AstraZeneca, participated in the advisory board for GSK, Pfizer, Roche and Novartis and received non-financial support from Pfizer, Roche, GSK, Novartis, and AstraZeneca. All remaining authors have declared no conflicts of interest.