9554 Background: Anti–PD-1 monotherapy yields limited response rates in Chinese patients with melanoma, highlighting the need for effective combination strategies. Elderly patients frequently present with multiple comorbidities and immunosenescence which may compromise both the efficacy and safety of immunotherapy. Thymosin α1 (Tα-1) promotes T-cell activation and survival, potentially enhancing responsiveness to immunotherapy, while exerting immunomodulatory effects during excessive inflammation that may reduce the risk of immune-related adverse events (irAEs). This study aimed to evaluate whether combining Tα-1 with toripalimab could improve efficacy while mitigating irAEs in elderly patients with advanced melanoma. Methods: This was a single-arm, open-label, Simon two-stage phase II study. Patients aged ≥60 years with pathologically confirmed unresectable stage III or IV melanoma and no prior immune checkpoint inhibitor exposure were enrolled. Treatment consisted of Tα-1 (1.6 mg daily during week 1, then three times weekly during weeks 2–3) plus toripalimab 240 mg intravenously every 3 weeks for up to four cycles, followed by toripalimab maintenance until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Stage I required ≥3 responses among 19 evaluable patients to proceed to Stage II. Results: Between July 2023 and September 2025, 19 patients were enrolled (median age 72 years, range 60–81). Acral melanoma accounted for 78.9% (n=15). All patients had chronic comorbidities; 63.2% had ECOG ≥2 and 47.4% had metastases in ≥3 organs. At a median follow-up of 10.5 months, ORR was 47.3% (95% CI, 22.6–72.1). Median PFS was 8.0 months (95% CI, 4.4–11.6), and median OS was not reached. Median PFS was 8.1 vs. 4.5 months in acral versus non-acral cutaneous melanoma (P=0.4). Elevated LDH showed a trend toward shorter PFS (2.8 vs. 8.1 months, P = 0.076). Six grade 1 irAEs were observed (vitiligo n=2, transaminase elevation n=2, thyroiditis n=2). Patients without progressive disease had lower neutrophil-to-lymphocyte ratios and higher lymphocyte percentages than those with PD. Conclusions: Tα-1 combined with toripalimab demonstrated promising efficacy and excellent tolerability in elderly patients with advanced melanoma. The prespecified criteria for Stage II expansion were met, and enrollment of an additional 36 patients is ongoing. Patient demographics. Characteristics No. of Patients (N=19) Age (median, range 72 (60-81) Male (%) 8 (42.1%) Melanoma subtype Acral 15 (78.9%) Cutaneous 4 (21.1%) NRAS status Wild type 14 (73.7%) Mutation 4 (21.1%) unknown 1 (5.3%) No. of organs with metastasis ≥3 9 (47.4%) Liver metastasis Yes 4 (21.1%) No 15 (78.9%) Brain metastasis Yes 2 (10.5%) No 17 (89.5%) ECOG PS 1 7 (36.8%) ≥2 12 (63.2%)
Wen et al. (Thu,) studied this question.