A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma

Daniel W. Bowles, Stephen B. Keysar, Justin R. Eagles, Guoliang Wang, Magdalena J. Glogowska, Jessica D. McDermott, Phuong N. Le, Dexiang Gao, Charles E. Ray, Paul J. Rochon, Dennis R. Roop, Aik Choon Tan, Hilary S. Serracino, Antonio Jimeno

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background This phase 1, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), antitumor activity, and molecular correlates of IPI-926, a Hedgehog pathway (HhP) inhibitor, combined with cetuximab in patients with relapsed/metastatic squamous cell carcinoma of the head and neck. Patients and methods Cetuximab was given with a 400 mg/m2 loading dose followed by 250 mg/m2 weekly. IPI-926 was given daily starting two weeks after cetuximab initiation. A "3 + 3" study design was used. Prior therapy with cetuximab was allowed. Tumor biopsies occurred prior to cetuximab initiation, prior to IPI-926 initiation, and after treatment with both drugs. Results Nine patients were enrolled. The RP2D was 160 mg, the same as the single-agent IPI-926 MTD. Among 9 treated, 8 evaluable patients, the best responses were 1 partial response (12.5%), 4 stable disease (50%), and 3 disease progressions (37.5%). The median progression free survival was 77 days (95% confidence interval 39-156). Decreases in tumor size were seen in both cetuximab-naïve patients (one HPV-positive, one HPV-negative). The most frequent treatment-emergent adverse events were fatigue, muscle cramps, and rash. No DLTs were observed. Tumor shrinkage and progression free survival were associated with intra-tumoral ERBB and HhP gene expression down-regulation during therapy, supporting the preclinical hypothesis. Conclusion Treatment with IPI-926 and cetuximab yielded expected toxicities with signs of anti-tumor activity. Serial tumor biopsies were feasible and revealed proof-of-concept biomarkers.

Original languageEnglish
Pages (from-to)74-79
Number of pages6
JournalOral Oncology
Publication statusPublished - 2016 Feb 1


  • Cetuximab
  • Combination therapy
  • Head and neck squamous cell carcinoma
  • Hedgehog signaling pathway
  • Phase 1

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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