Global Study Supports Penpulimab for First-Line Recurrent 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 study's design and its findings.

According to Shreenivas, this was a randomized Phase 3 study evaluating penpulimab plus chemotherapy versus chemotherapy and placebo as a first-line treatment for NPC. Previously, toripalimab (Loqtorzi) was the only FDA-approved agent in this setting. While other studies like JUPITER-02 (NCT03581786), CAPTAIN-1st (NCT03707509), and RATIONALE-309 had explored other agents, these were primarily conducted in Asia. This penpulimab study is notable for being a truly global trial, including sites in South America, the US, and Canada. Although enrollment was lower in non-Asian countries due to the lower incidence of NPC, the study played a crucial role in demonstrating the drug's efficacy outside of Asia.

The primary endpoint of this study, progression-free survival (PFS), was met at the interim analysis with statistical significance. The median PFS was 9.6 months in the penpulimab plus chemotherapy arm compared with 7 months in the placebo plus chemotherapy arm. Patients in the experimental arm also experienced a longer duration of response (9.8 months vs 5.6 months). The hazard ratio for PFS was 0.45, indicating a 55% reduction in the risk of disease progression.

The safety profile of the combination was manageable. Grade 3 or higher hematological toxicities were similar in both arms. Notably, the incidence of immune-related adverse events was low at 4.1%, potentially due to the agent's Fc-null function, which may mitigate these side effects. This manageable safety profile suggests broader applicability.

Furthermore, prespecified subgroup analyses demonstrated consistent efficacy across various subgroups, including patients with high or low PD-L1 expression, the presence or absence of liver metastases, and high or low EBV DNA levels.

"It's also important to note that this study has not given us the overall survival analysis. This was a crossover study, unlike some of the other studies in this space. It would be nice to see when the mature overall survival data is available," Shreenivas added in the interview.