153P - Combination of Tim-3 blockade TQB2618 with PD-1 blockade for patients with immunotherapy-resistant recurrent/metastatic nasopharyngeal carcinoma (R/M NPC): Preliminary results from a phase II study

Background

T cell immunoglobulin and mucin domain molecule 3 (Tim-3) is of overexpression in immunotherapy-resistant tumors. This single-arm, two-cohort, phase 2 study (NCT05563480) aimed to explore the efficacy and safety of TQB2618, a novel monoclonal antibody agent blockading Tim-3, plus PD-1 blockade penpulimab in subsequent-line treatment (cohort 1) of immunotherapy-resistant R/M NPC or in the first line by incorporating into chemotherapy (cohort 2) in treatment-naïve R/M NPC. Here, we report the preliminary results of cohort 1.

Methods

Eligible pts were diagnosed with histologically confirmed R/M NPC with ≥ 1 measurable lesion and had progressed on or after ≥ 1 line of platinum-based chemotherapy and PD-(L)1 immunotherapy. Pts were given penpulimab 200 mg and TQB2618 intravenously once per 3 weeks till disease progression or intolerance. Two TQB2618 dose levels of 1200 mg and 1500 mg were escalated initially according to the 3+3 design in a safety lead-in phase to determine the recommended dose in expansion phase. The primary aim of cohort 1 is to determine dose limiting toxicity (DLT) and tumor response.

Results

Between November 2022 and September 2023, 17 pts were enrolled (median [range] age, 49 [33–62] years; 41.2% women). The median previous treatment lines were 2 (range: 1–5). All pts developed metastasis and 7 (41.2%) were found liver lesions. The DLT was not observed, and 1500 mg was recommended for TQB2618. All pts received safety evaluation and 13 (76.5%) occurred at least one AE. The most common AEs were hypothyroidism (41.2%) and increased aspartate aminotransferase (23.5%). AEs of ≥ grade 3 or serious AEs were not observed. Seven pts had target lesions shrink although no one reached partial response. Nine pts obtained stable disease lasting for at least 4 weeks, given a disease control rate of 52.9%. The median PFS was 1.6 mo (95% CI, 0.0–3.2); 3 mo- and 6 mo-PFS was 27.3% and 18.2%, respectively. One pt was still on treatment after a follow-up for 14 months.

Conclusions

This novel dual-drug immunotherapy showed favorable safety profile, but the activity was limited in immunotherapy-resistant R/M NPC.

Clinical trial identification

NCT05563480.

Legal entity responsible for the study

The authors.

Funding

Chia Tai TianQing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.