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A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours

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CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid–drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile.


Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126.


Forty-three patients, median age 59 years (range 18–76; male = 27, female = 16), received one of ten dose levels (30–1600 mg/m2). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m2 on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure.


CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.

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The authors are grateful to the patients and their carers, who participated in this study and gratefully acknowledge the support of the study staff at the participating study sites.


The study was supported by Clavis Pharma ASA, Oslo, Norway. The Glasgow site was supported by the Glasgow ECMC (Experimental Cancer Medicine Centre), which is funded by Cancer Research UK, and the Chief Scientist’s Office, Scotland.

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Correspondence to B. Venugopal.

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B. Venugopal, A. Awada, S. Dueland, A. Hendlisz, S. Aamdal: None. T. R. J. Evans has received an honorarium for consultancy from Clovis for CO-1.01 (CP-4126) and research funding from Clavis Pharma and from Clovis Oncology for the conduct of this and subsequent studies. W. Rasch, K. Hernes and S. Hagen: Former employee at Clavis Pharma ASA.

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Venugopal, B., Awada, A., Evans, T.R.J. et al. A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours. Cancer Chemother Pharmacol 76, 785–792 (2015).

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