Combination of Tim-3 blockade TQB2618 with penpulimab and chemotherapy in the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma (R/M NPC): A multicenter, single-arm, two-cohort, phase 2 study.

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6031 Background: T cell immunoglobulin and mucin domain molecule 3 (Tim-3) is an inhibitory immune checkpoint receptor that negatively regulates the immune response. This multicenter, single-arm, two-cohort, phase 2 study (NCT05563480) aimed to explore the efficacy and safety of TQB2618, a novel monoclonal antibody blockading Tim-3, plus PD-1 blockade penpulimab as subsequent-line treatment in immunotherapy-resistant R/M NPC (cohort 1) or as first-line treatment by incorporating into chemotherapy in treatment-naïve R/M NPC (cohort 2). Here, we report the results of cohort 2. Methods: Eligible pts were ECOG PS 0–1, aged 18–70, diagnosed with histologically confirmed R/M NPC with ≥ 1 measurable lesion. Previous systemic treatment was not allowed, except as a part of curatively intended treatment for locoregionally advanced NPC and develop disease progression at least 6 months after last dose. TQB2618 and penpulimab were administered intravenously at doses of 1200 mg and 200 mg, respectively, on the first day of a 21-day cycle until disease progression or unacceptable toxicity while gemcitabine (1000 mg/m 2 , d1&8) and cisplatin (75mg/m 2 , d1) were given intravenously for the first 4–6 cycles. The primary endpoint is progression-free survival (PFS). Results: Between February 2023 and October 2023, 30 pts were enrolled (median [range] age, 52 [33–70] years; 16.7% women). Seventeen were diagnosed with metastatic disease at the first visit and others developed disease recurrence after definitive treatment. Liver metastasis was found in 10 pts. Median follow-up was 12.5 months (mo) (95% CI: 12.4–NE) at the data cut-off date on December 20, 2024. The median PFS reached 10.8 mo (95% CI, 9.6–16.4) and the 12 mo- and 15 mo-PFS were 40.9% and 34.1%, respectively. For the 17 pts with PD-L1 positive expression, the median PFS was 13.6 mo (95% CI: 8.4–16.6). The tumor response was complete response in 4 pts (13.3%), partial response in 21 pts (70.0%), stable disease in 4 pts (13.3%), and 1 could not be estimated, giving an objective response rate of 83.3%. A total of two pts died, both due to disease progression after 7.9 mo of enrollment. All pts experienced at least one adverse event (AE) and 25 pts (83.3%) were observed ≥ grade 3 (G3) AEs. The most common AEs of all grades (G1–4) or ≥ G3 were chemotherapy-related, including leukopenia (G1–4: 96.7%; ≥ G3: 40.0%), neutropenia (G1–4: 90.0%; ≥ G3: 36.7%), and anemia (G1–4: 93.3%; ≥ G3: 33.3%). Conclusions: To our knowledge, this is the first study to evaluate the addition of Tim-3 blockade to the standard first-line treatment of R/M NPC. The results demonstrated that this combination therapy provided clinical benefits comparable to those observed in the historical cohort treated with PD-1 blockade plus chemotherapy, while maintaining a manageable safety profile. Clinical trial information: NCT05563480 .

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