2. Academic Validation
  3. A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors

A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors

  • J Immunother Cancer. 2020 Mar;8(1):e000530. doi: 10.1136/jitc-2020-000530.
Aung Naing 1,  Justin F Gainor 2,  Hans Gelderblom 3,  Patrick M Forde 4,  Marcus O Butler 5,  Chia-Chi Lin 6,  Sunil Sharma 7,  Maria Ochoa de Olza 8,  Andrea Varga 9,  Matthew Taylor 10,  Jan H M Schellens 11,  Hongqian Wu 12,  Haiying Sun 12,  Antonio P Silva 13,  Jason Faris 14,  Jennifer Mataraza 14,  Scott Cameron 14,  Todd M Bauer 15 16
Affiliations

Affiliations

  • 1 MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org.
  • 2 Massachusetts General Hospital, Boston, Massachusetts, USA.
  • 3 Leiden University Medical Center, Leiden, The Netherlands.
  • 4 Johns Hopkins University, Baltimore, Maryland, USA.
  • 5 Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada.
  • 6 National Taiwan University Hospital, Taipei, Taiwan.
  • 7 Huntsman Cancer Institute, Salt Lake City, Utah, USA.
  • 8 Vall d'Hebron University Hospital, Barcelona, Spain.
  • 9 Gustave Roussy, Villejuif, France.
  • 10 Oregon Health & Science University, Portland, Oregon, USA.
  • 11 Utrecht University, Utrecht, The Netherlands.
  • 12 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
  • 13 Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • 14 Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • 15 Sarah Cannon Research Institute, Nashville, Tennessee, USA.
  • 16 Tennessee Oncology, PLLC, Nashville, Tennessee, USA.
PMID: 32179633 DOI: 10.1136/jitc-2020-000530
Abstract

Background: Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.

Methods: In the phase 1 part of the study, 58 patients received spartalizumab, intravenously, at doses of 1, 3, or 10 mg/kg, administered every 2 weeks (Q2W), or 3 or 5 mg/kg every 4 weeks (Q4W).

Results: Patients had a wide range of tumor types, most commonly sarcoma (28%) and metastatic renal cell carcinoma (10%); Other tumor types were reported in ≤3 patients each. Most patients (93%) had received prior antineoplastic therapy (median three prior lines) and two-thirds of the population had tumor biopsies negative for PD-L1 expression at baseline. The maximum tolerated dose was not reached. The recommended phase 2 doses were selected as 400 mg Q4W or 300 mg Q3W. No dose-limiting toxicities were observed, and adverse events included those typical of Other PD-1 antibodies. The most common treatment-related adverse events of any grade were fatigue (22%), diarrhea (17%), pruritus (14%), hypothyroidism (10%), and nausea (10%). Partial responses occurred in two patients (response rate 3.4%); one with atypical carcinoid tumor of the lung and one with anal Cancer. Paired tumor biopsies from patients taken at baseline and on treatment suggested an on-treatment increase in CD8+ lymphocyte infiltration in patients with clinical benefit.

Conclusions: Spartalizumab was well tolerated at all doses tested in patients with previously treated advanced solid tumors. On-treatment immune activation was seen in tumor biopsies; however, limited clinical activity was reported in this heavily pretreated, heterogeneous population. The phase 2 part of this study is ongoing in select tumor types.

Trial registration number: NCT02404441.

Keywords

clinical trials as topic; immunotherapy; programmed cell death 1 receptor.

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