Liposomal irinotecan plus nimotuzumab takes on immunotherapy-refractory NPC

In patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) refractory to immune checkpoint inhibitor (ICI) therapy, the combination of liposomal irinotecan plus nimotuzumab yields meaningful clinical activity while having favourable tolerability, as shown in a phase II study.

At a median follow-up of 9.25 months, the primary endpoint of objective response rate was 36.1 percent (95 percent confidence interval [CI], 20.8–53.8) among the 36 patients (median age 43 years, 86.1 percent male) who received the combination. [ESMO Asia 2025, abstract 670MO]

Of the patients, 13 had partial responses, nine had stable disease, 11 had progressive disease, and three were unevaluable. The disease control rate was 61.1 percent (95 percent CI, 43.5–76.9), and the median duration of response was 2.3 months (95 percent CI, 1.3–3.3).

The median progression-free survival was 3 months (95 percent CI, 2.1–3.9), while the median overall survival was not reached. At data cutoff, the 6-month overall survival rate was 82.6 percent.

A ≥50-percent reduction in plasma Epstein–Barr virus DNA at first post-treatment assessment correlated with higher objective response rate (p=0.046).

In terms of safety, grade ≥3 treatment-related adverse events occurred in 22.2 percent of patients. The most common were diarrhoea (8.3 percent), leukopenia (8.3 percent), and neutropenia (5.6 percent). No treatment-related deaths were reported.

These findings position liposomal irinotecan plus nimotuzumab as a viable treatment alternative, “particularly for patients who cannot tolerate high-intensity chemotherapy,” said first study author Dr Shuiqing He from Sun Yat-Sen University Cancer Center in Guangzhou, China.

Liposomal irinotecan is a topoisomerase I inhibitor formulated to enhance tumour accumulation, whereas nimotuzumab targets EGFR—which is highly expressed in NPC—to inhibit tumour proliferation and signalling. This combination regimen, according to He, has the potential to address the unmet clinical need in a high proportion of recurrent or metastatic NPC patients who progress after first-line immunotherapy, given that “current salvage therapies post-ICI offer limited efficacy and significant toxicity.”

The trial population included patients with pathologically confirmed recurrent or metastatic NPC who had progressed on at least one line of anti-PD-1 immunotherapy (monotherapy or combination), had at least one measurable lesion, and had ECOG PS score of 0 or 1.

Treatment consisted of two phases. In the combination phase, the patients received liposomal irinotecan at 70 mg/m² plus nimotuzumab at 400 mg, administered intravenously once every 2 weeks for up to 8 cycles. In the maintenance phase, the patients could continue receiving single-agent nimotuzumab at the discretion of the investigator until disease progression or unacceptable toxicity.