Glumetinib

BACKGROUND: Gallbladder adenocarcinoma (GBC) is an aggressive malignancy with poor prognosis and limited therapeutic options in advanced stages. Although MET amplification represents a potentially actionable molecular alteration, clinical evidence supporting MET-targeted therapy in GBC remains scarce. The potential synergistic effect of combining MET inhibition with immune checkpoint blockade is not well defined in this setting.Gallbladder adenocarcinoma (GBC) is an aggressive biliary malignancy with limited treatment options in advanced disease. MET amplification represents a potentially actionable alteration, yet clinical responses to MET inhibition in GBC are rarely reported. We describe a 70-year-old woman with advanced GBC who progressed on first-line chemotherapy plus immune checkpoint inhibition and subsequently showed only a brief response to second-line chemo–immunotherapy with targeted therapy. Molecular profiling identified high-level MET amplification, and third-line therapy with the selective MET inhibitor Glumetinib (200 mg daily) combined with envafolimab (200 mg every 3 weeks) was initiated. The largest lesion decreased from 80 × 88 mm prior to third-line therapy to 45 × 27 mm after two cycles, meeting criteria for partial response and remaining controlled through multiple cycles. Treatment interruption due to herpes zoster was followed by radiographic progression; subsequent biliary obstruction with infection precluded further systemic therapy, and the patient ultimately died. This case suggests that Glumetinib combined with PD-L1 blockade may provide clinically meaningful but time-limited benefit in MET-amplified GBC, supporting further evaluation in larger cohorts. CASE PRESENTATION: We report the case of a 70-year-old woman with advanced GBC who experienced disease progression following first-line chemotherapy combined with immune checkpoint inhibition and showed only transient benefit from second-line chemo-immunotherapy with targeted therapy. Comprehensive molecular profiling revealed high-level MET amplification. The patient subsequently received third-line treatment with the selective MET inhibitor Glumetinib (200 mg once daily) in combination with the PD-L1 inhibitor envafolimab (200 mg every 3 weeks). After two cycles, the largest tumor lesion decreased from 80 × 88 mm to 45 × 27 mm, achieving a partial response per RECIST criteria, with disease control maintained over multiple cycles. However, treatment interruption due to herpes zoster was followed by rapid disease progression. The clinical course was further complicated by biliary obstruction and infection, which precluded additional systemic therapy. The patient ultimately succumbed to disease progression. CONCLUSIONS: This case demonstrates that combined MET inhibition and PD-L1 blockade may induce a clinically meaningful tumor response in MET-amplified GBC, although the benefit appears to be limited in duration. These findings highlight the therapeutic potential of biomarker-driven combination strategies while underscoring the challenges of treatment durability and clinical management in advanced GBC. Further investigation in larger cohorts is warranted.