Penpulimab-kcqx extended progression-free survival to 9.6 months compared to 7.0 months with chemotherapy alone in patients with recurrent or metastatic nonkeratinizing nasopharyngeal carcinoma.
The U.S. Food and Drug Administration (FDA) approved the humanized IgG1 monoclonal anti–PD-1 antibody penpulimab-kcqx (Akeso Biopharma Co., Ltd.) in combination with cisplatin or carboplatin and gemcitabine as a first-line treatment for adults with recurrent or metastatic nonkeratinizing nasopharyngeal carcinoma (NPC). The agent was also approved as monotherapy for adults with metastatic nonkeratinizing NPC following progression on platinum-based chemotherapy and at least one additional systemic therapy.
The combination regimen was evaluated in Study AK105-304 (ClinicalTrials.gov identifier NCT04974398), a randomized, double-blind, multicenter trial. Investigators enrolled 291 patients with recurrent or metastatic NPC who had not received prior systemic chemotherapy for advanced disease into the study. Patients received either penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, followed by penpulimab-kcqx, or placebo with the same chemotherapy regimen, followed by placebo. Median progression-free survival, the primary endpoint, was 9.6 months in the penpulimab-kcqx group compared with 7.0 months in the control group. At 12 months, 31% of patients in the treatment arm and 11% in the control arm were alive and progression-free. Overall survival results were not mature; 70% of events needed for final analysis had occurred, with no negative trend observed.
Penpulimab-kcqx monotherapy was evaluated in Study AK105-202 (NCT03866967), an open-label, multicenter, single-arm trial. Researchers enrolled 125 patients with unresectable or metastatic NPC following progression on platinum-based chemotherapy and at least one additional therapy; the objective response rate was 28%, and median duration of response was not reached at the time of analysis.
Immune-mediated adverse events associated with penpulimab-kcqx included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions. In the combination setting, the most common adverse events (occurring in ≥ 20% of patients) were nausea, hypothyroidism, fatigue, rash, and COVID-19 infection; as a monotherapy, the most frequent events were hypothyroidism and musculoskeletal pain. Fatal adverse events occurred in 1% of patients.
Penpulimab-kcqx received fast track, breakthrough therapy, and orphan drug designations from the FDA.
Source: FDA