Penpulimab (PD-1 inhibitor) combined with platinum-based chemotherapy as induction therapy for newly diagnosed thymic carcinoma: A multicenter, single-arm, phase II trial.

8120 Background: Our retrospective study showed that immune checkpoint inhibitors plus chemotherapy had encouraging anti-tumor activity and durable response for unresectable thymic carcinoma (TC). This prospective clinical trial aimed to evaluate the efficacy and safety of penpulimab—a humanized anti-PD-1 monoclonal antibody—in combination with platinum-based chemotherapy as induction therapy for patients with newly diagnosed TC. Methods: Patients with histologically confirmed TC at Masaoka stage II–IV, an ECOG performance status of 0 or 1, and no history of prior systemic anticancer therapy were enrolled. Following 4 cycles of induction therapy with penpulimab penpulimab (200 mg), carboplatin (AUC 5 mg/mL per min), and nab-paclitaxel (260 mg/m²) administered intravenously every 3 weeks, patients were re-evaluated by a multidisciplinary team (MDT). Subsequent treatment was stratified based on resectability: operable patients proceeded to surgery, whereas inoperable patients received standard radiotherapy or chemotherapy. Based on a Fleming two-stage design, the treatment would be promising if at least 10 of the first 18 evaluable patients in stage I or at least 14 of the 36 evaluable patients at the end of stage II have a confirmed response. The primary endpoint was objective response rate (ORR) evaluated by independent central review. Results: Between June 2023 and July 2025, 18 eligible patients were enrolled. Fourteen patients (77.8%) had WHO stage IV disease. Ten patients achieved a partial response (PR), meeting the predefined efficacy threshold for early termination according to the Fleming design. The ORR and disease control rate (DCR) were 55.6% and 94.5% respectively in the overall population, with corresponding rates of 57.1% and 92.8% in the subgroup with stage IV disease. Nine patients underwent surgical resection, including 6 with stage IV disease, and an R0 resection was achieved in 7 cases. Among the 9 patients who underwent surgery, one patient (11.1%) with stage III disease achieved a pathological complete response (pCR), and another patient (11.1%) with stage IV disease achieved a major pathological response (MPR). At a median follow-up of 20.15 months, the 1-year relapse-free survival (RFS) and overall survival (OS) rates were 72.2% and 88.9% for the entire population, and 64.3% and 78.6% for patients with stage IV disease, respectively. The most common adverse events of grade 3 or worse were neutropenia (44.4%), anemia (16.7%), and hepatotoxicity (11.2%). One patient died from immune-mediated myocarditis with concurrent hepatitis and myasthenia gravis. Conclusions: Penpulimab combined with platinum-based chemotherapy showed promising antitumour activity in previously untreated TC, with vigilance required for immune-mediated myocarditis. Clinical trial information: ChiCTR2300076314.