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A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.

Publication ,  Journal Article
Mettu, NB; Ulahannan, SV; Bendell, JC; Garrido-Laguna, I; Strickler, JH; Moore, KN; Stagg, R; Kapoun, AM; Faoro, L; Sharma, S
Published in: Clin Cancer Res
March 1, 2022

PURPOSE: TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) is a co-inhibitory receptor of T-cell and natural killer cell activity. Targeting TIGIT with or without PD-1/PD-L1 checkpoint inhibition may enhance antitumor immunity. PATIENTS AND METHODS: This Phase 1a/b trial was a first-in-human, open-label, multicenter, dose-escalation and -expansion study in patients with locally advanced or metastatic solid tumors. Using 3 + 3 design, patients underwent 14-day treatment cycles with anti-TIGIT antibody etigilimab alone (Phase 1a; 0.3, 1.0, 3.0, 10.0, 20.0 mg/kg intravenously) or in combination with anti-PD-1 antibody nivolumab (Phase 1b; 3.0, 10.0, 20.0 mg/kg etigilimab and 240 mg nivolumab). Primary objective was safety and tolerability. RESULTS: Thirty-three patients were enrolled (Phase 1a, n = 23; Phase 1b, n = 10). There were no dose-limiting toxicities (DLT). MTD for single and combination therapy was not determined; maximum administered dose was 20 mg/kg. The most commonly reported adverse events (AE) were rash (43.5%), nausea (34.8%), and fatigue (30.4%) in Phase 1a and decreased appetite (50.0%), nausea (50.0%), and rash (40%) in Phase 1b. Six patients experienced Grade ≥3 treatment-related AEs. In Phase 1a, 7 patients (30.0%) had stable disease. In Phase 1b, 1 patient had a partial response; 1 patient had prolonged stable disease of nearly 8 months. Median progression-free survival was 56.0 days (Phase 1a) and 57.5 days (Phase 1b). Biomarker correlative analyses demonstrated evidence of clear dose-dependent target engagement by etigilimab. CONCLUSIONS: Etigilimab had an acceptable safety profile with preliminary evidence of clinical benefit alone and in combination with nivolumab and warrants further investigation in clinical trials.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 1, 2022

Volume

28

Issue

5

Start / End Page

882 / 892

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasms, Second Primary
  • Nausea
  • Humans
  • Exanthema
  • Antineoplastic Combined Chemotherapy Protocols
  • Antibodies, Monoclonal
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
 

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Mettu, N. B., Ulahannan, S. V., Bendell, J. C., Garrido-Laguna, I., Strickler, J. H., Moore, K. N., … Sharma, S. (2022). A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors. Clin Cancer Res, 28(5), 882–892. https://doi.org/10.1158/1078-0432.CCR-21-2780
Mettu, Niharika B., Susanna V. Ulahannan, Johanna C. Bendell, Ignacio Garrido-Laguna, John H. Strickler, Kathleen N. Moore, Robert Stagg, Ann M. Kapoun, Leonardo Faoro, and Sunil Sharma. “A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.Clin Cancer Res 28, no. 5 (March 1, 2022): 882–92. https://doi.org/10.1158/1078-0432.CCR-21-2780.
Mettu NB, Ulahannan SV, Bendell JC, Garrido-Laguna I, Strickler JH, Moore KN, et al. A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors. Clin Cancer Res. 2022 Mar 1;28(5):882–92.
Mettu, Niharika B., et al. “A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.Clin Cancer Res, vol. 28, no. 5, Mar. 2022, pp. 882–92. Pubmed, doi:10.1158/1078-0432.CCR-21-2780.
Mettu NB, Ulahannan SV, Bendell JC, Garrido-Laguna I, Strickler JH, Moore KN, Stagg R, Kapoun AM, Faoro L, Sharma S. A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors. Clin Cancer Res. 2022 Mar 1;28(5):882–892.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 1, 2022

Volume

28

Issue

5

Start / End Page

882 / 892

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasms, Second Primary
  • Nausea
  • Humans
  • Exanthema
  • Antineoplastic Combined Chemotherapy Protocols
  • Antibodies, Monoclonal
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences