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616 Pharmacokinetics and safety of a subcutaneous formulation of nivolumab (NIVO SC) monotherapy: updated results from the phase 1/2 CheckMate 8KX study
  1. Sara Lonardi1,
  2. Iwona Ługowska2,
  3. Anne O’Donnell3,
  4. Christopher Jackson4,
  5. Loes Maria Latten-Jansen5,
  6. Richard North6,
  7. Marcelo Garrido Salvo7,
  8. Armando Santoro8,
  9. Matías Chacón9,
  10. Linghui Li10,
  11. Devanand Joseph11,
  12. Elizabeth Gibson11,
  13. Bryan Bennett12,
  14. Balmeet Gurm11,
  15. Wee-Teck Ng13,
  16. R Donald Harvey14,
  17. José Manuel Trigo Pérez15 and
  18. Aitana Calvo16
  1. 1Veneto Institute of Oncology IRCCS, Padova, Italy
  2. 2Department of Early Phase Clinical Trials, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
  3. 3Wellington Hospital, Wellington, New Zealand
  4. 4Dunedin Hospital, Dunedin, New Zealand
  5. 5Department of Internal Medicine, Division of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, Netherlands
  6. 6Tauranga Hospital, Tauranga, New Zealand
  7. 7Pontificia Universidad Católica, Clinica San Carlos de Apoquindo, Las Condes, Chile
  8. 8Department of Biomedical Sciences, Humanitas University, Milan, Italy
  9. 9Department of Medical Oncology, Instituto Alexander Fleming, Buenos Aires, Argentina
  10. 10Bristol Myers Squibb, Arlington, MA, USA
  11. 11Bristol Myers Squibb, Princeton, NJ, USA
  12. 12Bristol Myers Squibb, Uxbridge, United Kingdom
  13. 13Bristol Myers Squibb, Boudry, Neuchâtel, Switzerland
  14. 14Emory University, Atlanta, GA, USA
  15. 15Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Spain
  16. 16Hospital General Universitario Gregorio Marañón, Madrid, Spain
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background NIVO administered via intravenous (IV) infusion is a transformative immuno-oncology therapy across multiple tumor types. However, there remains an unmet need to decrease the burden of oncology treatment for patients, healthcare facilities, and healthcare professionals (HCPs). SC administration may alleviate these challenges, is typically preferred over IV infusions by patients and HCPs, and improves healthcare resource utilization by decreasing preparation and chair time and reducing administrative burden.1 Previously reported results from CheckMate 8KX had <17 months follow-up.2 We present analyses with extended follow-up from CheckMate 8KX (NCT03656718), a phase 1/2 study investigating NIVO SC ± the permeation enzyme recombinant human hyaluronidase PH20 (rHuPH20).

Methods Enrolled patients were immune checkpoint inhibitor-naïve, eligible for NIVO monotherapy, and had advanced solid tumors, including non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, and colorectal cancer. Study design is shown in figure 1. The primary endpoint was to describe the pharmacokinetics of NIVO SC ± rHuPH20 by non-compartmental analyses. Secondary endpoints included the safety and immunogenicity of NIVO SC. Exploratory endpoints included patient-reported outcomes and efficacy.

Results A total of 139 patients were treated. Median (range) age was 66 (24–93) years, 33.8% of patients were female, and patients had an ECOG performance status of 0 (38.1%) or 1 (61.9%). The most common tumor type was NSCLC (27.3%), and most patients (56.1%) had one prior line of therapy. Minimum follow-up is shown in figure 1. Pharmacokinetic data are shown in table 1. Most treatment-related adverse events were low-grade (table 2). Few patients developed anti-drug antibodies (ADAs), and no patients developed neutralizing ADAs (table 1). ORR data across all parts will be presented. Responding to an experience and preference questionnaire, most patients reported high satisfaction with SC administration, preferring it over IV administration, and noted limited pain associated with SC injection (table 3).

Conclusions The pharmacokinetics of NIVO SC was well characterized. NIVO SC was well tolerated, with a safety and ADA profile consistent with NIVO IV. Patients were highly satisfied with SC administration and preferred it over IV infusion. These data support the evaluation of NIVO SC + rHuPH20 in the ongoing phase 3 randomized noninferiority study, CheckMate 67T (NCT04810078).

Trial Registration NCT03656718

References 1. O’Shaughnessy J, Sousa S, Cruz J et al. Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. Eur J Cancer. 2021;152:223–232.

2. Lonardi S, Ługowska I, Jackson C et al. CheckMate 8KX: phase 1/2 multi-tumor preliminary analyses of a subcutaneous formulation of nivolumab (± rHuPH20). Poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 4–8, 2021.

Ethics Approval This study was conducted in accordance with the Declaration of Helsinki and the international guidelines for Good Clinical Practice. The independent ethics committee or institutional review board of each participating study centre approved the protocol and all amendments.

Consent Written informed consent was obtained from all patients.

Abstract 616 Figure 1

Study design

Abstract 616 Table 1

Summary of pharmacokinetic and ADA data

Abstract 616 Table 2

Safety summary

Abstract 616 Table 3

Patient-reported outcomes

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