Skip to main content

Advertisement

SpringerLink
Log in

Exposure–response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To investigate camidanlumab tesirine (Cami) exposure–response (E–R) relationships, using an integrated population pharmacokinetic model, for patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma enrolled in an open-label, phase 1 study (NCT02432235).

Methods

Exploratory analyses investigated relationships between exposure measures (Cmaxss, Cminss, and Cavgss) and the occurrence of binary variables (overall response rate [ORR] and selected adverse events [AEs]) and nonbinary variables (overall survival [OS]).

Results

Exploratory analyses showed a significant, positive relationship between exposure and ORR/OS. The final model showed this effect was non-significant due to the covariate effects. Cami exposures were higher in patients with selected grade ≥ 2 AEs at cycle 6 (the anticipated steady-state exposure level), confirmed in the final E–R models.

Conclusions

Based on univariate results, Cmaxss was used as the exposure measure in all models, except for the autoimmune AE full E–R model in which Cavgss was used. The positive relationship between exposure and ORR/OS (higher exposure significantly associated with higher probabilities of ORR/OS) was not statistically significant in the final models. The final safety E–R models demonstrated a significant positive association between Cami exposure and selected grade ≥ 2 AEs, with higher exposures associated with higher probabilities of experiencing the grade ≥ 2 AEs at cycle 6. The results identify preliminary predictors of efficacy and safety and provide a basis for a dosing rationale and benefit–risk profile of Cami in patients with relapsed/refractory cHL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability statement

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

References

  1. Jiang M, Bennani NN, Feldman AL (2017) Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol 10:239–249. https://doi.org/10.1080/17474086.2017.1281122

    Article  CAS  Google Scholar 

  2. Thandra KC, Barsouk A, Saginala K, Padala SA, Barsouk A, Rawla P (2021) Epidemiology of non-Hodgkin’s lymphoma. Med Sci (Basel). https://doi.org/10.3390/medsci9010005

    Article  Google Scholar 

  3. Collaboration; GBoDC, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 3:524–548. https://doi.org/10.1001/jamaoncol.2016.5688

    Article  Google Scholar 

  4. Ansell SM (2018) Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol 93:704–715. https://doi.org/10.1002/ajh.25071

    Article  Google Scholar 

  5. Flynn MJ, Zammarchi F, Tyrer PC, Akarca AU, Janghra N, Britten CE et al (2016) ADCT-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Mol Cancer Ther 15:2709–2721. https://doi.org/10.1158/1535-7163.MCT-16-0233

    Article  CAS  Google Scholar 

  6. Hamadani M, Collins GP, Caimi PF, Samaniego F, Spira A, Davies A et al (2021) Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol 8:e433–e445. https://doi.org/10.1016/S2352-3026(21)00103-4

    Article  Google Scholar 

  7. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3068. https://doi.org/10.1200/JCO.2013.54.8800

    Article  Google Scholar 

  8. Food and Drug Administration (1999) Guidance for industry: population pharmacokinetics. http://www.fda.gov/downloads/drugs/guidances/UCM072137.pdf. Accessed 21 Feb 2022

  9. Food and Drug Administration (2003) Guidance for industry: exposure response relationships. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072109.pdf. Accessed 21 Feb 2022

  10. European Medicines Agency (2007) Committee for medicinal products for human use (CHMP). Guideline on reporting the results of poulation pharmacokinetic analyses. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003067.pdf. Accessed 2 Feb 2022

  11. Goto N, Tsurumi H, Goto H, Shimomura YI, Kasahara S, Hara T et al (2012) Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens. Ann Hematol 91:705–714. https://doi.org/10.1007/s00277-011-1363-4

    Article  CAS  Google Scholar 

  12. Gupta M, Stenson M, O’Byrne M, Maurer MJ, Habermann T, Cerhan JR et al (2016) Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Ralpha as predictors of event-free survival in T-cell lymphoma. Ann Oncol 27:165–172. https://doi.org/10.1093/annonc/mdv486

    Article  CAS  Google Scholar 

  13. Lindqvist CA, Christiansson LH, Simonsson B, Enblad G, Olsson-Stromberg U, Loskog AS (2010) T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies. Immunology 131:371–376. https://doi.org/10.1111/j.1365-2567.2010.03308.x

    Article  CAS  Google Scholar 

  14. Wang L, Liao DZ, Zhang J, Xia ZJ, Peng XW, Lu Y (2013) Clinical significance of serum soluble interleukin-2 receptor-alpha in extranodal natural killer/T-cell lymphoma (ENKTL): a predictive biomarker for treatment efficacy and valuable prognostic factor. Med Oncol 30:723. https://doi.org/10.1007/s12032-013-0723-4

    Article  CAS  Google Scholar 

  15. Ambrosy AP, Vaduganathan M, Huffman MD, Khan S, Kwasny MJ, Fought AJ et al (2012) Clinical course and predictive value of liver function tests in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the Everest trial. Eur J Heart Fail 14:302–311. https://doi.org/10.1093/eurjhf/hfs007

    Article  CAS  Google Scholar 

  16. Giannini EG, Testa R, Savarino V (2005) Liver enzyme alteration: a guide for clinicians. CMAJ 172:367–379. https://doi.org/10.1503/cmaj.1040752

    Article  Google Scholar 

  17. Herrera A, Carlo-Stella C, Collins G, Maddocks K, Bartlett N, Savage K et al (2020) Preliminary results of a phase 2 study of camidanlumab tesirine (Cami), a novel pyrrolobenzodiazepine-based antibody-drug conjugate, in patients with relapsed or refractory Hodgkin lymphoma. Blood 136:21–23. https://doi.org/10.1182/blood-2020-137451

    Article  Google Scholar 

  18. clinicaltrials.gov Study to evaluate the efficacy and safety of camidanlumab tesirine (ADCT-301) in patients with relapsed or refractory Hodgkin lymphoma (NCT04052997). https://clinicaltrials.gov/ct2/show/NCT04052997. Accessed 5 Jan 2022

  19. Toukam M, Wuerthner J, Havenith K, Hamadani M, Caimi PF, Kopotsha T et al. Population pharmacokinetics analysis of Camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. https://doi.org/10.1007/s00280-022-04486-4

Download references

Acknowledgements

Medical writing support was provided by Claire Line, PhD, on behalf of CiTRUS Health Group, which was in accordance with Good Publication Practice (GPP3) guidelines. This support was funded by ADC Therapeutics SA.

Funding

This study was funded by ADC Therapeutics SA.

Author information

Authors and Affiliations

  1. ADC Therapeutics America, Inc., Murray Hill, NJ, USA

    Marie Toukam & Joseph P. Boni

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

    Mehdi Hamadani

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

    Paolo F. Caimi

  4. ADC Therapeutics SA, Épalinges, Switzerland

    Hans G. Cruz & Jens Wuerthner

Authors
  1. Marie Toukam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph P. Boni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehdi Hamadani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo F. Caimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans G. Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jens Wuerthner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marie Toukam.

Ethics declarations

Conflict of interest

M Toukam and J Boni are currently employed and current equity holders at ADC Therapeutics America, Inc., 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 Pharma. 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. HG Cruz and J Wuerthner are currently employed and current equity holders at ADC Therapeutics SA, a publicly traded company.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2563 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toukam, M., Boni, J.P., Hamadani, M. et al. Exposure–response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol 91, 1–12 (2023). https://doi.org/10.1007/s00280-022-04487-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-022-04487-3

Keywords

Search

Navigation