Motolimod plus standard chemotherapy and cetuximab (EXTREME regimen) was well tolerated, but did not lead to improvements in survival outcomes among most patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), according to a study published in JAMA Oncology.1

Previous studies have demonstrated that motolimod — a toll-like receptor 8 (TLR8) agonist — can induce positive immune responses, but whether it could improve outcomes in the first-line setting with the EXTREME regimen among patients with R/M SCCHN has yet to be fully investigated.

For the phase 2 Active8 ( Identifier: NCT01836029) study, researchers randomly assigned 195 patients to receive the EXTREME regimen (carboplatin or cisplatin, fluorouracil, cetuximab) plus placebo or motolimod every 3 weeks for 6 cycles. Patients continued to receive weekly cetuximab with either placebo or motolimod every 4 weeks thereafter.

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Results showed that median progression-free survival (PFS) was 6.1 months among patients treated with motolimod compared with 5.9 months for patients who received placebo (hazard ratio [HR], 0.99;  1-sided 90% CI, 0.00-1.22; P = .47). The median overall survival (OS) was 13.5 months and 11.3 months for motolimod and placebo, respectively (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P = .40).

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Patients treated with motolimod had an increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash.

A pre-specified subgroup revealed however, that motolimod significantly prolonged survival outcomes among patients who were human papillomavirus-positive; PFS was 7.8 months compared with 5.9 months among patients treated with placebo (HR, 0.58; 1-sided 90% CI, 0.00-0.90; P = .046) and OS was 15.2 months versus 12.6 months (HR, 0.41; 1-sided 90% CI, 0.00-0.77; P = .03).

In an exploratory analysis, patients who experienced injection site reactions had improved PFS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P = .06) and OS (18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P = .02).

The authors concluded that “results provide important information regarding patient selection for treatment with TLR8 agonists and suggest that further evaluation in HPV-positive oropharyngeal cancer may be warranted.”


  1. Ferris RL, Saba NF, Gitlitz BJ, et al. Effect of adding motolimod to standard combination chemotherapy and cetuximab treatment of patients with squamous cell carcinoma of the head and neck [published online June 21, 2018]. JAMA Oncol. doi:10.1001/jamaoncol.2018.1888