Dr Shreenivas on the FDA Approval of Penpulimab Plus Chemo for Frontline Non-Keratinizing Nasopharyngeal Carcinoma

“The AK105-304 study evaluating penpulimab supports its potential as the second FDA-approved agent for use in the first-line treatment of non-keratinizing nasopharyngeal carcinoma, demonstrating a reasonably tolerable safety profile.”

Aditya Shreenivas, MD, MS, an assistant professor in Head & Neck Medical Oncology at City of Hope, discussed the FDA approval of penpulimab-kcqx plus chemotherapy for the frontline treatment of non-keratinizing nasopharyngeal carcinoma (NPC).

The approval was supported by findings from the phase 3 AK105-304 trial (NCT04974380), which enrolled patients with previously untreated, advanced non-keratinizing NPC and randomly assigned them to receive either penpulimab—a PD-1 inhibitor—or placebo in combination with standard chemotherapy. The study met its prespecified primary end point at the first interim analysis, demonstrating a statistically significant improvement in progression-free survival (PFS) with penpulimab (HR, 0.45; 95% CI, 0.33-0.62; 2-sided P < .0001). Patients in the penpulimab arm achieved a median PFS of 9.6 months (95% CI, 7.1-12.5) compared with 7.0 months (95% CI, 6.9-7.3) in the placebo group.

Prior to this approval, toripalimab-tpzi (Loqtorzi) was the only PD-1 inhibitor with FDA approval for NPC, though other PD-1 agents such as tislelizumab (Tevimbra) and camrelizumab have been approved in other regulatory jurisdictions. Shreenivas noted that the penpulimab approval marks the second PD-1 inhibitor cleared in the United States for this indication and supports the expanding role of immunotherapy in the management of virus-associated head and neck cancers.

The safety profile of penpulimab was consistent with other agents in the PD-1 class and was considered tolerable, Shreenivas added. These findings further establish immune checkpoint blockade as a foundational component of first-line therapy in this disease setting.

Shreenivas emphasized that the FDA approval of penpulimab plus chemotherapy may also enable further clinical development of penpulimab in other NPC settings, including early-stage or recurrent disease. He noted that this regulatory milestone underscores the feasibility of global collaboration in bringing novel immunotherapeutics to patients in the Untied States with rare cancers such as NPC.