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Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma

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Abstract

Purpose

The objective of this analysis was to develop a population pharmacokinetic (PPK) model to characterize camidanlumab tesirine (Cami) pharmacokinetics based on the phase 1 study in relapsed/refractory lymphoma (NCT02432235).

Methods

An initial PPK model was developed based on a two-compartment model with parallel linear and nonlinear elimination pathways. Pharmacokinetic parameters were evaluated for correlation with potential demographic covariates; significant covariates were retained in the final model.

Results

In the final PPK model, baseline weight effects were included on clearance (CL), intercompartmental clearance (Q), and the volumes of distribution in the central (V1) and peripheral (V2) compartments. The baseline soluble CD25 (sCD25) effect was included on CL and maximum velocity of saturable clearance (Vmax); sex effect was included on CL and V1; and ethnicity effect was included on deconjugation clearance (CLdec). For a typical patient, CL and CLdec were 0.516 and 0.21 L/day, respectively (tAb elimination half-life: 18.72 days); V1 and V2 were 4.41 and 2.67 L, respectively; Vmax was 0.49 mg/day; the Michaelis–Menten constant (Km) was 0.409 µg/mL; and the first-order rate for decrease of Vmax (KDES) was 0.0197/day. Cami exposure was higher for patients with low baseline sCD25, higher body weight, and females.

Conclusions

The final model described the observed data well, estimates of PK parameters were obtained, and covariates with significant effects on Cami exposure were identified. Altogether, this final PPK model provides a robust basis for analysis of Cami exposure–response relationships and further supports identification of the optimal Cami dosing schedule for patients with relapsed/refractory lymphoma.

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Data Availability

Summary trial information for study NCT02432235 is available online. Requests regarding data collected for the study should be sent to clinical.trials@adctherapeutics.com.

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Acknowledgements

Medical writing support was provided by Adrianne Spencer, Ph.D. (CiTRUS Health Group), and was funded by ADC Therapeutics (Murray Hill, NJ) in accordance with Good Publication Practice (GPP3) guidelines.

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Authors and Affiliations

  1. ADC Therapeutics, Murray Hill, NJ, USA

    Marie Toukam & Joseph P. Boni

  2. ADC Therapeutics SA, Épalinges, Switzerland

    Jens Wuerthner & Hans G. Cruz

  3. ADC Therapeutics (UK) Limited, London, UK

    Karin Havenith & Tim Kopotsha

  4. BMT and Cellular Therapy Program, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Mehdi Hamadani

  5. Department of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Paolo F. Caimi

Authors
  1. Marie Toukam
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  2. Jens Wuerthner
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  3. Karin Havenith
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  4. Mehdi Hamadani
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  5. Paolo F. Caimi
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  6. Tim Kopotsha
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Correspondence to Marie Toukam.

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Conflict of interest

M Toukam is currently employed and a current equity holder at ADC Therapeutics America, Inc., a publicly traded company. J Wuerthner is currently employed and a current equity holder at ADC Therapeutics SA, a publicly traded company. K Havenith is currently employed and a current equity holder at ADC Therapeutics (UK) Ltd, a publicly traded company. M Hamadani reports consultancy with Janssen R&D, Incyte Corporation, ADC Therapeutics, Celgene Corporation, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Seagen, Genmab, Novartis, and Kite; membership on an entity’s board of directors or advisory committees for ADC Therapeutics; research funding from Takeda Pharmaceutical Company, Spectrum Pharmaceuticals, and Astellas Pharma; and speakers bureau memberships for Sanofi Genzyme, AstraZeneca, BeiGene, and Kite. PF Caimi reports advisory board memberships for Amgen, Bayer, Kite Pharma, ADC Therapeutics, Novartis, and Genentech; research funding for ADC Therapeutics and Genentech; and speakers bureau membership for Celgene. T Kopotsha is currently employed and a current equity holder at ADC Therapeutics (UK) Ltd, a publicly traded company. HG Cruz is currently employed and a current equity holder at ADC Therapeutics SA, a publicly traded company. JP Boni is currently employed and a current equity holder at ADC Therapeutics America, Inc., a publicly traded company.

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Toukam, M., Wuerthner, J., Havenith, K. et al. Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol 91, 13–24 (2023). https://doi.org/10.1007/s00280-022-04486-4

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