Ferris RL, et al. - The Active8 study (a multicenter, randomized, double-blind, placebo-controlled clinical trial) was conducted to assess if outcomes for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) can be improved by motolimod in combination with standard therapy. In the intent-to-treat population, adding motolimod to a platinum (carboplatin or cisplatin), fluorouracil, and cetuximab (the EXTREME regimen) was well tolerated but did not improve progression-free survival (PFS) or overall survival (OS). Researchers observed significant benefit in human papillomavirus (HPV)-positive patients and those with injection site reactions, implying that toll-like receptor 8 (TLR8) stimulation might benefit subset- and biomarker-selected patients.

Methods

• Study participants were adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015; follow-up ended September 2016, and between June 2016 and December 2017, analysis for the present report was conducted.
• For this investigation, combination treatment with platinum (carboplatin or cisplatin), fluorouracil, cetuximab (the EXTREME regimen), and either placebo or motolimod, each administered intravenously every 3 weeks.
• Study participants received a maximum of 6 chemotherapy cycles, after which they received weekly cetuximab with either placebo or motolimod every 4 weeks.
• Main outcome and measure analyzed was progression-free survival (PFS) as determined by independent central review using immune-related RECIST (Response Evaluation Criteria in Solid Tumors).
• Overall survival (OS) and safety were included key secondary end points.

Results

• Out of 195 recruited patients, 85% were men (n = 166); 82% were white (n = 159), median age was 58 years (range 23-81 years).
• It was observed that median PFS was 6.1 vs 5.9 months (hazard ratio [HR], 0.99; 1-sided 90% CI, 0.00-1.22; P=.47), and median OS was 13.5 vs 11.3 months (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P=.40) for motolimod vs placebo.
• With motolimod, increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash were noted.
• Out of 83 cases oropharyngeal cancer, 52 (63%) were human papillomavirus (HPV) positive.
• Motolimod vs placebo resulted in significantly longer PFS (7.8 vs 5.9 months; HR, 0.58; 1-sided 90% CI, 0.00-0.90; P=.046) and OS (15.2 vs 12.6 months; HR, 0.41; 1-sided 90% CI, 0.00-0.77; P=.03) in a prespecified subgroup analysis of HPV-positive participants.
• Patients with injection site reactions had longer PFS and OS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P=.06; and median OS, 18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P=.02) in an exploratory analysis.