Penpulimab — Drug Monograph

Drug class: Checkpoint Inhibitor

Mechanism of Action

Humanized IgG1 anti-programmed cell death protein 1 (PD-1) monoclonal antibody engineered with an Fc region modified to eliminate FcγR binding (and thus ADCC/ADCP of effector T cells) while retaining high-affinity, slow-off-rate PD-1 blockade. By preventing PD-1 from engaging PD-L1/PD-L2, penpulimab restores cytotoxic T-cell activity against tumor cells.

FDA Indications

• First-line treatment of recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC), in combination with cisplatin (or carboplatin) and gemcitabine (approved April 23, 2025)
• Recurrent or metastatic non-keratinizing nasopharyngeal carcinoma with disease progression on or after platinum-based chemotherapy and at least one other prior line, as a single agent

Common Side Effects

• Anemia
• Nausea
• Decreased appetite
• Fatigue
• Constipation
• Hypothyroidism
• Rash
• Pyrexia

Clinical Pearl

Penpulimab-kcqx is the first FDA-approved therapy specifically for nasopharyngeal carcinoma. Its Fc-silent engineering is designed to avoid depleting the very effector T cells it aims to activate. It is used first-line with gemcitabine/platinum and as monotherapy in the platinum-pretreated setting.

Related Therapies & Mechanisms

• Atezolizumab (Tecentriq) — Checkpoint Inhibitor
• Avelumab (Bavencio) — Checkpoint Inhibitor
• Cemiplimab (Libtayo) — Checkpoint Inhibitor
• Cosibelimab (Unloxcyt) — Checkpoint Inhibitor