Personalized Biomarker-Based Umbrella Trial in Recurrent or Metastatic HNSCC

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In a Korean phase II trial (KCSG HN 15-16 TRIUMPH) reported in the Journal of Clinical Oncology, Keam et al described results of a personalized biomarker-driven umbrella trial for the treatment of patients with platinum-refractory recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) using matched molecular targeted agents.

Study Details

In the multicenter trial, targeted next-generation sequencing was performed between October 2017 and August 2020 in 203 patients. Patients were assigned to treatments on the basis of matching genomic profiles, receiving either:

  • Alpelisib, a PIK3CA inhibitor (n = 45; 33 in response-analysis set)
  • Poziotinib, an EGFR/HER2 inhibitor (n = 17; n = 13 in analysis set)
  • Nintedanib, a FGFR inhibitor (n = 10; 7 in analysis set)
  • Abemaciclib, a CDK4/6 inhibitor (n = 34; 23 in analysis set).

If no matching target was identified, patients received durvalumab, a PD-L1 inhibitor (n = 73).

Patients with disease progression in the first four groups were permitted to cross over to durvalumab (n = 36), yielding a total of 109 in the durvalumab group (90 in response-analysis set). Patients with disease progression on durvalumab could cross over to durvalumab plus the cytotoxic T-cell lymphocyte-4 inhibitor tremelimumab (n = 51; 50 in the analysis set).

The primary endpoint was disease control rate in the alpelisib group and objective response rate in the other groups on investigator assessment.

Key Findings

The disease control rate in the alpelisib group was 65.6% and the objective response rate was 21.2%.

Objective response rates were 0% in the poziotinib group, 42.9% in the nintedanib group, 0% in the abemaciclib group, and 15.6% in the durvalumab group. The objective response rate in the crossover durvalumab/tremelimumab group was 2.2%.   

In the alpelisib, poziotinib, nintedanib, abemaciclib, and durvalumab groups, median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months, respectively, and median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months. 

Toxicities were manageable, and no treatment-related deaths were reported.

The investigators concluded, “To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that next-generation sequencing–based genomic phenotyping was methodologically feasible and applicable.”

Hwan Jung Yun, MD, of the Department of Internal Medicine, Chungnam National University Hospital, Daejeon, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Korean National R&D Program for Cancer Control, Ministry of Health and Welfare. For full disclosures of the study authors, visit

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