Phase II study of mirogabalin for oxaliplatin-associated chemotherapy-induced peripheral neuropathy in gastrointestinal cancer: The SmiliNg trial.

12057 Background: Oxaliplatin is a key drug in the treatment of unresectable advanced or recurrent gastrointestinal (GI) cancers, however, chemotherapy-induced peripheral neuropathy (CIPN) often limits its use. Mirogabalin is an oral gabapentinoid that alleviates neuropathic pain by binding to the α2δ subunit of voltage-gated calcium channels, but evidence regarding the efficacy of mirogabalin for CIPN induced by oxaliplatin remains insufficient. SmiliNg trial evaluated the efficacy and safety of mirogabalin in patients with unresectable advanced or recurrent GI cancers who have oxaliplatin-associated CIPN. Methods: This single-center, single-arm exploratory phase II trial enrolled patients with unresectable or recurrent GI cancer who were receiving ongoing first-line oxaliplatin-based chemotherapy or continuing fluoropyrimidine-based therapy after discontinuation of oxaliplatin, and who had painful CIPN (including numbness/tingling) with a numerical rating scale (NRS) score of ≥ 4. Mirogabalin was administered orally twice daily and titrated weekly according to Cockcroft–Gault creatinine clearance. The primary endpoint was the change in 24-hour average pain NRS from baseline to week 6. Secondary endpoints included PRO-CTCAE-assessed improvement in numbness/tingling, adverse events (CTCAE v5.0), and attainment of maintenance dose. The planned sample size was 30 patients. Clinical trial information: UMIN000049555. Results: Between February 2023 and April 2025, 30 patients were enrolled. The median age was 64 years (range, 36–83), with female patients accounting for 33%. The primary cancer types included colorectal (n=17), small bowel (n=7), gastric (n=6), and esophageal (n=1) cancers. The Mean baseline 24-hour pain NRS was 5.80 (SD 1.97). The mean change from baseline at week 6 was −1.46 (SD 2.66) (p = 0.010; 90% CI −2.35 to −0.57) , thereby the prespecified primary endpoint was achieved. The proportions of ≥1 -point responders were 58%. On the PRO-CTCAE, the proportions of patients achieving a ≥1-category improvement in worst severity were 38% and 38% at weeks 3 and 6, respectively; the corresponding proportions for interference with daily activities were 34% and 27%. Maintenance-dose attainment rates at weeks 3 and 6 were 59% and 68%, respectively. The most common adverse events were somnolence (83%) and dizziness (38%). Grade ≥3 adverse events comprised AST/ALT increased, and pulmonary infection, each occurring in one patient; none were related to mirogabalin treatment. Conclusions: This study suggests that mirogabalin is effective and well-tolerated for the management of moderate-to-severe painful CIPN during oxaliplatin-based chemotherapy. These findings warrant further evaluation in a confirmatory trial. Clinical trial information: 000049555.