A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

Martina Puglisi; L Rhoda Molife; Maja Ja de Jonge; Khurum H Khan; Leni van Doorn; Martin D Forster; Montserrat Blanco; Martin Gutierrez; Catherine Franklin; Todd Busman; Jianning Yang; Ferry Alm Eskens

doi:10.2217/fon-2021-0140

A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

Future Oncol. 2021 Jul;17(21):2747-2758. doi: 10.2217/fon-2021-0140. Epub 2021 Apr 14.

Affiliations

¹ Drug Development Unit, Institute of Cancer Research/The Royal Marsden, Downs Road, Sutton, Surrey, SM2 5PT, UK.
² Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
³ UCL Cancer Institute, University College London Hospital, Gower Street, London, WC1E 6BT, UK.
⁴ John Theurer Cancer Center, Hackensack University Medical Center, 92 2nd St, Hackensack, NJ 07601, USA.
⁵ AbbVie, Inc, 1 North Waukegan Road, North Chicago, IL 60064, USA.

PMID: 33849298
DOI: 10.2217/fon-2021-0140

Abstract

Aim: This Phase I study investigated safety of navitoclax and docetaxel in patients (n = 41) with advanced solid tumors. Patients & methods: Two navitoclax plus docetaxel dosing schedules (21 and 28 days) were evaluated. Maximum tolerated dose, dose-limiting toxicities and preliminary antitumor activity were assessed. Results: Ten (24%) patients experienced dose-limiting toxicities; dose-escalation cohorts: n = 7 (21-day schedule: n = 5; 28-day schedule: n = 2) and 21-day expanded safety cohort: n = 3. Navitoclax 150-mg days 1-5 every 21 days with docetaxel 75 mg/m² day 1 was the maximum tolerated dose and optimal schedule. Adverse events included thrombocytopenia (63%), fatigue (61%), nausea (59%) and neutropenia (51%). Four confirmed partial responses occurred. Conclusion: Navitoclax 150-mg orally once/day was safely administered with docetaxel. Myelosuppression limited dose escalation; antitumor activity was observed. Clinical trial registration: NCT00888108 (ClinicalTrials.gov).

Keywords: ABT-263; Phase I; apoptosis; docetaxel; navitoclax.

Publication types

Clinical Trial, Phase I
Multicenter Study

MeSH terms

Administration, Oral
Adult
Aged
Aged, 80 and over
Aniline Compounds / administration & dosage
Aniline Compounds / adverse effects*
Aniline Compounds / pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects*
Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
Docetaxel / administration & dosage
Docetaxel / adverse effects*
Docetaxel / pharmacokinetics
Drug Administration Schedule
Fatigue / chemically induced
Fatigue / epidemiology
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Nausea / chemically induced
Nausea / epidemiology
Neoplasms / drug therapy*
Neutropenia / chemically induced
Neutropenia / epidemiology
Sulfonamides / administration & dosage
Sulfonamides / adverse effects*
Sulfonamides / pharmacokinetics
Thrombocytopenia / chemically induced
Thrombocytopenia / epidemiology

Substances

Aniline Compounds
Sulfonamides
Docetaxel
navitoclax

Associated data

ClinicalTrials.gov/NCT00888108

Grants and funding

AbbVie