After the FDA Approval: Next Steps for Penpulimab in NPC

The FDA approval penpulimab for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) as a single agent and in combination with cisplatin or carboplatin and gemcitabine in April 2025. In an interview with Targeted Oncology^TM, Aditya Shreenivas, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, at City of Hope and an investigator of the phase 3 Study AK105-304 (NCT04974398) that supported the approval, discusses the benefits penpulimab offers over the standard of care and where research is headed for this agent.

While cross-trial comparisons should be interpreted cautiously, the hazard ratio for progression-free survival in this study was notably impressive at 0.45, appearing slightly better than some other agents in this setting. Additionally, the rate of grade 3 immune-related adverse events was lower at 4.1% compared with what was observed with toripalimab (Loqtorzi) in the JUPITER-02 study (NCT03581786). These aspects are particularly noteworthy, according to Shreenivas.

Furthermore, this was a truly global study, unlike JUPITER-02 which included no non-Asian patients and lacked a crossover design. Offering a crossover option in contemporary trials is often preferred and receives greater support from patient groups, Shreenivas explained.

This study was funded and supported by Akeso Bio, a China-based company developing multiple compounds. Future research could explore novel combinations with penpulimab to further improve response rates and progression-free survival.

Interestingly, Shreenivas notes that PD-L1 did not appear to be the most effective predictive marker in this study, as responses were observed across different PD-L1 levels. Therefore, identifying more informative biomarkers to better select patients for these combination therapies is crucial. Analyzing historical factors like metastasis sites and EBV DNA from the subgroup analysis could yield further insights. It's also important to note that overall survival data is not yet available from this crossover study, making the mature OS results highly anticipated.

"I would like to thank all the investigators who are involved, all patients that were involved with this study and Akeso Bio, and also my home institution, City of Hope," Shreenivas added in the interview.