Multicenter phase 2 trial of penpulimab and gemcitabine with or without anlotinib in metastatic nasopharyngeal carcinoma

A multicenter phase 2 trial in China employed a three-cohort, two-phase design to evaluate the potential of anlotinib as a substitute for cisplatin in gemcitabine-penpulimab combinations for metastatic nasopharygeal carcinoma (mNPC) in patients who were previously treated with cisplatin-based chemoradiotherapy. During the lead-in phase of the trial patients were randomized 1:1:1 to one of three treatment arms: gemcitabine, cisplatin, penpulimab, and anlotinib (GP-PA; n=8), gemcitabine, cisplatin, and penpulimab (GP-P; n=6), or gemcitabine, penpulimab, and anlotinib (GAP; n=6). The expansion phase enriched the optimal cohort, with stratification based on PD-L1 expression. Primary endpoints were safety and objective response rate. In the lead-in phase, grade ≥ 3 treatment-emergent adverse events occurred in 87.5% (GP-PA), 100% (GP-P), and 66.7% (GAP) patients. At median 20.2 months follow-up, median PFS/OS were 4.1/18.4 months for GP-PA and not reached for GP-P and GAP. In the expansion phase, 14 patients received GAP, with an ORR of 93.3% and grade ≥ 3 TEAEs in 71.4% of patients. At data cutoff point, the median PFS had not been reached, and 12-month PFS and OS rates were 53.8% and 78.6%, respectively. The authors conclude that the GAP regimen demonstrated a favorable safety and efficacy profile compared to the GP-PA and GP-P regimens in patients with mNPC, suggesting that substituting anlotinib for cisplatin may offer a viable therapeutic strategy for this patient population.