MIZAR-003 Extended Follow-up Selected for ESMO 2026 LBA, GC101 Shows Sustained PFS Benefit

After progression following anti-PD-1 treatment, options in the backend setting for advanced melanoma remain limited. Conventional TIL therapy requires intensive lymphodepletion and IL-2 support, imposing high requirements for clinical implementation and safety management. In a prior randomized phase III study, 168 patients with unresectable stage IIIC or IV melanoma were randomized 1:1 to TIL or ipilimumab. Median PFS was 7.2 months in the TIL group and 3.1 months in the ipilimumab group, with HR=0.50 (95%CI 0.35~0.72); the primary endpoint was PFS [Peer-reviewed·K]. GC101-related registration information shows that MIZAR-003 is a randomized, open-label phase II study sponsored by Shanghai Juncell Therapeutics, with a planned or actual enrollment of 98 participants and a recruiting status ^[1]. The reported figure of 98 cases differs from the 18 cases in the registry (media-exclusive). It was described in the news as a pivotal phase II study, with continuous inclusion in ASCO and ESMO LBA; these figures are media-exclusive (needs verification).

The extended ESMO follow-up used a data cutoff date of 2026年7月2日. Median PFS was 4.37 months in the GC101 group and 1.61 months in the chemotherapy group, with HR=0.44 (95%CI 0.28~0.70, P=0.0004) (media-exclusive). ORR increased from 42.0% to 44.0% in the GC101 group, compared with 8.2% in the chemotherapy group, and 3 additional cases of complete response in target lesions were reported (media-exclusive). In the mucosal subgroup, median PFS was 4.81 months and 1.45 months in the two groups, respectively, with HR=0.23 and P=0.0215 (media-exclusive). In the acral subgroup, median PFS was 4.37 months and 1.38 months, respectively, with HR=0.41 and P=0.0034 (media-exclusive). OS data are not yet mature; 59% of patients in the chemotherapy group crossed over to GC101 treatment, and a favorable but unconfirmed survival trend was observed in the GC101 group (media-exclusive) (needs verification).

Compared with the ASCO results, this follow-up was extended by approximately 1.5 months. The PFS benefit was sustained, ORR increased, 3 cases of complete response in target lesions were observed in the update, and statistically significant PFS improvements were shown in both the acral and mucosal subgroups (media-exclusive). Regarding safety, grade ≥3 adverse events in the GC101 group remained dominated by hematologic toxicity related to lymphodepletion conditioning; no treatment-related deaths or grade ≥3 cytopenias lasting longer than 30 days occurred, and extended follow-up did not identify new safety signals (media-exclusive). The regimen uses lower-intensity lymphodepletion, with the cyclophosphamide dose reduced by approximately half, hydroxychloroquine substituted for fludarabine, and post-infusion IL-2 support eliminated. Contemporary randomized phase III literature supports only the PFS efficacy of TIL in advanced melanoma and the treatment framework of non-lymphodepletion chemotherapy followed by cell infusion combined with high-dose IL-2. The independent mechanistic effects of reducing lymphodepletion and eliminating IL-2 with GC101 still require validation [Peer-reviewed·K] (needs verification).

Complete OS analyses, the impact of crossover treatment on between-group survival comparisons, long-term survival benefits, and detailed safety results for each subgroup have not yet been disclosed. Registration information indicates that the primary completion date for MIZAR-003 was 2026年5月12日, with the most recent update on 2026年8月5日; the specific data remain subject to subsequent formal publication or updates ^[1] (media-exclusive) (needs verification).

Not all the above figures were traced to primary sources and require verification. The figure 003 was not traced to a primary source and was not marked as media-exclusive; 4.37 was not traced to a primary source and was not marked as media-exclusive; 1.61 was not traced to a primary source and was not marked as media-exclusive; 0.44 could not be found in the materials; 0.28 was not traced to a primary source and was not marked as media-exclusive; 0.70 was not traced to a primary source and was not marked as media-exclusive; 0.0004 was not traced to a primary source and was not marked as media-exclusive; 4.81 was not traced to a primary source and was not marked as media-exclusive (needs verification).