Penpulimab Gains NMPA Approval for First-Line Treatment of Recurrent or Metastatic NPC

Penpulimab (formerly AK105), an anti–PD-1 monoclonal antibody, has received approval from the National Medical Products Administration (NMPA) for use in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (NPC). This approval expands the clinical utility of penpulimab, which was previously approved for third-line treatment in advanced NPC, establishing its role across multiple lines of therapy for this patient population.1

“In China, there remains a significant unmet clinical need for NPC. As the only IgG1 subtype anti–PD-1 monoclonal antibody globally, penpulimab has demonstrated robust efficacy in clinical studies, enhancing the effectiveness of immunotherapy for NPC. The approval for first-line treatment marks a major milestone, as it provides a comprehensive treatment regimen for clinicians and patients, benefiting a large population of NPC patients in China, from first-line to third-line therapy,” Chaosu Hu, PhD, a clinical investigator in the Department of Radiation Oncology at Fudan University Shanghai Cancer Center in China, explained in a news release.

The efficacy and safety of penpulimab plus gemcitabine in combination with cisplatin or anlotinib (AL3818) was evaluated in a phase 2 trial (NCT04736810) as first-line treatment for patients with advanced NPC.2 Patients in cohorts A, B, and C received gemcitabine, cisplatin, penpulimab, and anlotinib; gemcitabine, cisplatin, and penpulimab; and gemcitabine, penpulimab, and anlotinib, respectively.

Preliminary findings from the trial demonstrated that among patients enrolled in cohort C (n = 7), one patient achieved a confirmed complete response (CR), while all others had confirmed partial responses (PRs). The objective response rate (ORR) in this cohort was 100%, compared with 80.0% in cohorts A (n = 5) and B (n = 5).

The safety analysis showed that replacing cisplatin with anlotinib resulted in a lower incidence of grade 3 or higher adverse effects (AEs). Grade 3 or higher AEs were reported in 85.7% (n = 6) of patients in cohort A, 100% (n = 5) in cohort B, and 57.1% (n = 4) in cohort C. Additionally, the overall incidence of serious AEs was 28.6%, 20.0%, and 14.3% in cohorts A, B, and C, respectively. The most common grade 3 or higher AEs observed across all cohorts were decreased white blood cell count and decreased neutrophil count.

“Penpulimab has demonstrated a significantly high response rate and prolonged survival benefits in both first-line treatment of NPC and in patients with metastatic NPC who have failed multiple lines of prior therapy. Additionally, it has shown a favorable safety profile, with a low incidence of immune-related AEs,” Chen Xiaozhong, MD, a professor at Zhejiang Cancer Hospital in Hangzhou, China, added.1

Phase 2 Trial Design

Investigators enrolled patients with histologically confirmed regional or distant metastatic NPC who had at least one measurable lesion per RECIST 1.1 criteria.2 Eligible patients were required to be between 18 and 75 years of age, have an ECOG performance status of 0 or 1, and have received no prior systemic therapy for metastatic disease.

Patients were randomly assigned to one of three treatment cohorts. Gemcitabine was given at a dose of 1000 mg/m² on days 1 and 8 and cisplatin was administered at a dose of 80 mg/m² on day 1 for 4 to 6, 3-week cycles. Penpulimab was administered intravenously at a dose of 200 mg on day 1 and oral anlotinib was given at a dose of 12 mg once daily on days 1 through 14 until confirmed disease progression, unacceptable toxicities, or for a maximum duration of 2 years.

Patients experiencing disease progression but demonstrating clinical benefit were permitted to continue penpulimab and anlotinib at the physician’s discretion.

The trial’s primary end point was ORR. Secondary end points included progression-free survival, overall survival, duration of response, disease control rate, and safety/tolerability.

A Tumor-Agnostic Future for Penpulimab

Beyond NPC, penpulimab has secured three additional indications, including first-line treatment of locally advanced or metastatic squamous non–small cell lung cancer in combination with chemotherapy and monotherapy for relapsed or refractory classical Hodgkin lymphoma following at least two prior lines of systemic chemotherapy.1

Additionally, a supplemental new drug application is currently under review for penpulimab in combination with anlotinib for the first-line treatment of patients with advanced hepatocellular carcinoma, further underscoring its potential in a broader range of malignancies.

References

1. Akeso’s penpulimab receives NMPA approval for first-line treatment of nasopharyngeal cancer. News release. Akeso, Inc. March 16, 2025. Accessed March 18, 2025. https://www.akesobio.com/en/media/akeso-news/20250317/
2. Huang S, Chen X, Qu S, et al. Penpulimab plus gemcitabine in combination with cisplatin or anlotinib as first-line treatment for metastatic nasopharyngeal carcinoma (M NPC): a phase II study. J Clin Oncol. 2022;40(suppl 16):e18032. doi:10.1200/JCO.2022.40.16_suppl.e18032