FDA Approval Sought for Penpulimab in Third-Line Metastatic Nasopharyngeal Carcinoma

A biologics license application has been submitted to the FDA for the PD-1 monoclonal antibody penpulimab for the third-line treatment of patients with metastatic nasopharyngeal carcinoma.

A biologics license application (BLA) has been submitted to the FDA for the PD-1 monoclonal antibody penpulimab (formerly AK105) for the third-line treatment of patients with metastatic nasopharyngeal carcinoma.1

The application will be assessed under the Real-Time Oncology Review (RTOR) process, which seeks to accelerate the drug approval process; notably, this marks the first PD-1 agent from China to undergo BLA review by the FDA under RTOR.

Penpulimab is a late-stage, differentiated humanized monoclonal antibody against PD-1. The agent was developed to eliminate fragment crystallizable (Fc) receptor–binding activity, particularly with regard to FcγR, and it has been shown to successfully eradicate undesirable effects that are mediated by the Fc receptor.2 Through this elimination, the agent has improved antitumor activity and a slower antigen binding off rate compared with current PD-1 antibodies on the market.

The agent is under investigation in patients with metastatic nasopharyngeal carcinoma with disease progression following 2 or more previous therapies, including platinum-containing chemotherapy, as part of the multicenter, single-arm, open-label, phase 2 AK105-202 trial (NCT03866967).3

To participate, patients needed to be between the ages of 18 years and 70 years, an ECOG performance status of 0 or 1, an expected life expectancy of at least 3 months, and at least 1 measurable lesion per RECIST v1.1 criteria.4 They could not be candidates for radical local therapy, and they needed to have stage IVB metastatic disease for which frontline platinum-based chemotherapy and second-line chemotherapy as failed. Patients also needed to have acceptable organ function to enroll.

If they received their last radiotherapy or antitumor treatment within 4 weeks before the first dose of study drug; had previously been exposed to an anti–PD-1, anti­–PD-L1, anti–CTLA-4 agent or any other antibody or treatment for T-cell co-stimulatory pathways; had other invasive malignancies within 5 years; had active, known, or suspected autoimmune diseases or a medical history of autoimmune illness, they were excluded.

The primary end point of the trial was objective response rate (ORR) based on RECIST v1.1 criteria and per independent review committee (IRC) assessment. Key secondary end points comprised disease control rate (DCR), progression-free survival, and duration of response (DOR).

Investigators also examined PD-L1 expression in archived tissues, and those with a tumor proportion score of at least 50% were determined to have PD-L1 positivity. Biomarker correlative analysis were also done through the collection of plasma Epstein-Barr virus DNA.

As of September 18, 2020, the median follow-up was 7.9 months and penpulimab was found to elicit an ORR of 27.0% (95% CI, 19.0%-36.3%) per IRC assessment in a total of 111 efficacy-evaluable patients with progressive disease following 2 or more previous lines of therapy. In those with PD-L1–positive disease, the ORR was even higher, at 39.5% (95% CI, 25.0%-55.6%); this rate was lower in those with PD-L1 negativity, at 19.7% (95% CI, 10.9%-31.3%).

Moreover, the PD-1 monoclonal antibody resulted in a DCR of 49.5% (95% CI, 39.9%-59.2%) in this patient population. The median DOR had not yet been reached (0.95+ to 11.43+), and the estimated 6-month DOR rate was 85.6% (95% CI, 52.5%-96.3%).

Regarding safety, 79.2% of 130 patients reported treatment-related toxicities, with 14.6% (n = 19) experiencing grade 3 or higher effects. Four patients (3.1%) discontinued treatment with the agent. Serious adverse effects determined to be associated with the treatment were reported in 10.0% (n = 13) of patients.

The most common treatment-related adverse effects (TRAEs) experienced with penpulimab included fever (24.5%), hypothyroidism (24.6%), anemia (23.1%), increased alanine aminotransferase (17.0%), and decreased white blood cell count (10.8%). Grade 3 or higher TRAEs included abnormal hepatic function (2.3%) and anemia (2.3%).


  1. Akeso’s penpulimab monoclonal antibody submitted BLA in the United States. News release. Akeso, Inc. May 24, 2021. Accessed May 24, 2021. https://prn.to/3oP5PkP
  2. Products center: penpulimab. Akesobio website. Akeso, Inc. Accessed May 24, 2021. https://bit.ly/3ytNYo9
  3. Chen X, Wang W, Zou Q, et al. 804 a phase II study of the anti-programmed cell death-1 (PD-1) antibody penpulimab in patients with metastatic nasopharyngeal carcinoma (NPC) who had progressed after two or more lines of chemotherapy. Journal for ImmunoTherapy of Cancer. 2020;8. doi:10.1136/jitc-2020-SITC2020.0804
  4. A study of anti-PD-1 AK105 in patients with metastatic nasopharyngeal carcinoma. ClinicalTrials.gov. Updated March 7, 2019. Accessed May 24, 2021. https://clinicaltrials.gov/ct2/show/NCT03866967