Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck

J Immunother Cancer. 2023 Aug;11(8):e007141. doi: 10.1136/jitc-2023-007141.

Abstract

Background: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

Methods: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes.

Results: Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration.

Conclusions: Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration.

Trial registration number: NCT03162731.

Keywords: Head and Neck Neoplasms; Immunotherapy; Ipilimumab; Nivolumab; Radiotherapy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Ipilimumab / pharmacology
  • Ipilimumab / therapeutic use
  • Nivolumab* / pharmacology
  • Nivolumab* / therapeutic use
  • Squamous Cell Carcinoma of Head and Neck / drug therapy

Substances

  • Nivolumab
  • Ipilimumab
  • B7-H1 Antigen

Associated data

  • ClinicalTrials.gov/NCT03162731