Phase I/II study of tecemotide as immunotherapy in Japanese patients with unresectable stage III non-small cell lung cancer

Lung Cancer. 2017 Mar:105:23-30. doi: 10.1016/j.lungcan.2017.01.007. Epub 2017 Jan 17.

Abstract

Objectives: Unresectable stage III NSCLC (non-small cell lung cancer) confers a poor prognosis and interest is growing in the use of immunotherapy to improve outcomes for patients with this disease. We investigated the safety and efficacy of maintenance tecemotide, a mucin 1 (MUC1)-specific agent that induces T-cell responses to MUC1, versus placebo in Japanese patients with stage III unresectable NSCLC and no disease progression after primary chemoradiotherapy.

Materials and methods: Patients aged ≥20 years with unresectable stage III NSCLC, stable disease or clinical response after primary chemoradiotherapy and performance status ≤1, were recruited across 25 centers in Japan. Patients were randomized 2:1 to tecemotide (930μg as lipopeptide) or placebo subcutaneously once weekly for 8 weeks, then every 6 weeks until disease progression or treatment withdrawal. Cyclophosphamide 300mg/m2 (maximum dose 600mg) was given intravenously 3days before the first dose of tecemotide. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, time to progression, time to treatment failure and safety.

Results: The intent-to-treat population comprised 172 patients; 114 received tecemotide and 58 placebo. Baseline characteristics were comparable between treatment arms. Most patients (94%) received primary concurrent chemoradiotherapy. There was no apparent trend toward increased OS time with tecemotide over placebo (median 32.4 versus 32.2 months, hazard ratio 0.95, 95% confidence interval 0.61-1.48; P=0.83). No improvements in secondary efficacy endpoints were observed. The frequency of treatment-related adverse events was similar, and serious adverse event rates were the same in both arms. There were no new safety signals.

Conclusions: These results do not support those from a randomized phase III study (START) of improved OS with tecemotide in the subgroup of patients treated with primary concurrent chemoradiotherapy.

Keywords: Immunotherapy; MUC1; Non-small cell lung cancer; Primary chemoradiotherapy; Tecemotide.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunotherapy / methods
  • Japan
  • Lung Neoplasms / drug therapy*
  • Male
  • Membrane Glycoproteins / administration & dosage*
  • Membrane Glycoproteins / therapeutic use
  • Middle Aged
  • Neoplasm Staging
  • Survival Analysis
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • L-BLP25
  • Membrane Glycoproteins
  • Cyclophosphamide