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Targeted Oncology

, Volume 10, Issue 1, pp 111–123 | Cite as

Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study

  • Irene Brana
  • Antonio Calles
  • Patricia M. LoRusso
  • Lorrin K. Yee
  • Thomas A. Puchalski
  • Shobha Seetharam
  • Bob Zhong
  • Carla J. de BoerEmail author
  • Josep Tabernero
  • Emiliano Calvo
Original Research

Abstract

C-C chemokine ligand 2 (CCL2) stimulates tumor growth, metastasis, and angiogenesis. Carlumab, a human IgG1κ anti-CCL2 mAb, has shown antitumor activity in preclinical and clinical trials. We conducted a first-in-human phase 1b study of carlumab with one of four chemotherapy regimens (docetaxel, gemcitabine, paclitaxel + carboplatin, and pegylated liposomal doxorubicin HCl [PLD]). Patients had advanced solid tumors for which ≥1 of these regimens was considered standard of care or for whom no other treatment options existed. Dose-limiting toxicities included one grade 4 febrile neutropenia (docetaxel arm) and one grade 3 neutropenia (gemcitabine arm). Combination treatment with carlumab had no clinically relevant pharmacokinetic effect on docetaxel (n = 15), gemcitabine (n = 12), paclitaxel or carboplatin (n = 12), or PLD (n = 14). Total serum CCL2 concentrations increased post-treatment with carlumab alone, consistent with carlumab-CCL2 binding, and continued increase in the presence of all chemotherapy regimens. Free CCL2 declined immediately post-treatment with carlumab but increased with further chemotherapy administrations in all arms, suggesting that carlumab could sequester CCL2 for only a short time. Neither antibodies against carlumab nor consistent changes in circulating tumor cells (CTCs) or circulating endothelial cells (CECs) enumeration were observed. Three of 19 evaluable patients showed a 30 % decrease from baseline urinary cross-linked N-telopeptide of type I collagen (uNTx). One partial response and 18 (38 %) stable disease responses were observed. The most common drug-related grade ≥3 adverse events were docetaxel arm—neutropenia (6/15) and febrile neutropenia (4/15); gemcitabine arm—neutropenia (2/12); paclitaxel + carboplatin arm—neutropenia, thrombocytopenia (4/12 each), and anemia (2/12); and PLD arm—anemia (3/14) and stomatitis (2/14). Carlumab could be safely administered at 10 or 15 mg/kg in combination with standard-of-care chemotherapy and was well-tolerated, although no long-term suppression of serum CCL2 or significant tumor responses were observed.

Keywords

Carlumab Chemokine CCL2 Combination chemotherapy Clinical trial Phase 1 Solid tumors 

Notes

Acknowledgments

Gianna Paone and Jennifer Han of Janssen Scientific Affairs, LLC, provided assistance with writing, editing, preparing, and submitting this manuscript. Janssen Research & Development, LLC, provided funding for the study. This trial was registered at ClinicalTrials.gov, NCT01204996.

Conflict of interest

Drs. Puchalski, Seetharam, Zhong, and de Boer are employees of Janssen, own stock in Johnson & Johnson, and/or are currently conducting research sponsored by Janssen. Antonio Calles is a Rio Hortega fellowship grant recipient from the Instituto de Salud Carlos III (CM09/00283). All remaining authors have declared no conflicts of interest.

Supplementary material

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Irene Brana
    • 1
  • Antonio Calles
    • 2
    • 3
  • Patricia M. LoRusso
    • 4
  • Lorrin K. Yee
    • 5
    • 6
  • Thomas A. Puchalski
    • 7
  • Shobha Seetharam
    • 7
  • Bob Zhong
    • 7
  • Carla J. de Boer
    • 8
    Email author
  • Josep Tabernero
    • 1
  • Emiliano Calvo
    • 2
  1. 1.Vall d’Hebron University Hospital and Institute of Oncology (VHIO)Universitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.START MadridCentro Integral Oncológico Clara CampalMadridSpain
  3. 3.Clinical Research ProgrammeSpanish National Cancer Research Centre (CNIO)MadridSpain
  4. 4.Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  5. 5.Northwest Medical SpecialtiesTacomaUSA
  6. 6.Vista OncologyOlympiaUSA
  7. 7.Janssen Research & Development, LLCSpring HouseUSA
  8. 8.Janssen Biologics, BVLeidenThe Netherlands

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