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Penpulimab Approved For Nonkeratinizing Nasopharyngeal Carcinoma

The Food and Drug Administration (FDA) has approved penpulimab-kcqx, a programmed death receptor-1 (PD-1)-blocking antibody, in combination with either cisplatin or carboplatin and gemcitabine, for the first-line treatment of adults with recurrent or metastatic nonkeratinizing nasopharyngeal carcinoma (NPC); or as a single agent, for the treatment of adults with metastatic nonkeratinizing NPC with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. 

The approval of penpulimab-kcqx as first-line treatment was based on the randomized, double-blind AK105-304 trial (ClinicalTrials.Gov Identifier: NCT04974398), which included 291 participants with recurrent NPC with local-regional recurrence and/or distant metastasis occurring at least 6 months after curative intent treatment completion, or with primary metastatic NPC not suitable for local therapy at time of diagnosis. 

Study participants were randomly assigned 1:1 to receive penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, followed by single-agent penpulimab-kcqx; or placebo with cisplatin or carboplatin and gemcitabine, followed by single-agent placebo until disease progression or unacceptable toxicity or for a maximum of 24 months. The primary endpoint was progression-free survival (PFS), as assessed by a Blinded Independent Review Committee according to RECIST v1.1.

Findings showed that the risk of disease progression or death was reduced by 55% with penpulimab-kcqx compared with placebo (hazard ratio, 0.45 [95% CI, 0.33-0.62]; P <.0001). Median PFS was 9.6 months (95% CI, 7.1-12.5) in the penpulimab-kcqx group vs 7.0 months (95% CI, 6.9-7.3) in the placebo group. After 12 months of follow-up, 31% and 11% of patients in the penpulimab-kcqx and placebo arms, respectively, were alive and progression free. At the time of analysis, overall survival (key secondary endpoint) data were not mature. 

The approval of penpulimab-kcqx as a single-agent for NPC was based on the open-label, single-arm AK105-202 study (ClinicalTrials.Gov Identifier: NCT03866967), which included 125 participants with unresectable or metastatic non-keratinizing NPC who had progressed after platinum-based chemotherapy and at least 1 other line of therapy.

Study participants received single-agent penpulimab-kcqx until disease progression or unacceptable toxicity for a maximum of 24 months. The primary endpoints were objective response rate (ORR) and duration of response (DOR), as assessed by an Independent Radiology Review Committee according to RECIST v1.1.

Results showed the ORR was 28% (95% CI, 20-37), with 27% of responders achieving a partial response. The median DOR was not reached (95% CI, 9.2, not estimable); 46% of patients had a DOR of 12 months or greater. 

The most common adverse reactions reported with penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia. As a single-agent, the most common adverse reactions reported were anemia and hypothyroidism.

Penpulimab-kcqx is supplied as a 10mg/mL solution in a single-dose vial. The recommended dosage is 200mg intravenously over 60 minutes every 3 weeks (combination with cisplatin or carboplatin and gemcitabine) or 2 weeks (as a single agent) until disease progression or unacceptable toxicity, for a maximum of 24 months. 

FDA Approves Akeso's PD-1 Monoclonal Antibody For Recurrent Or Metastatic Non-Keratinizing Nasopharyngeal Carcinoma

Approval of penpulimab-kcqx marks the company's US regulatory debut and introduces a new immunotherapy option for advanced nasopharyngeal carcinoma.

Image Credit: Adobe Stock Images/SKT Studio

The FDA has approved Akeso's penpulimab-kcqx, a PD-1 monoclonal antibody, for two indications treating nasopharyngeal carcinoma (NPC). The drug is now indicated in combination with chemotherapy as a first-line treatment for adult patients with recurrent or metastatic non-keratinizing NPC and as a monotherapy for patients with metastatic NPC who have progressed following platinum-based chemotherapy and at least one additional line of therapy.1

"We are very excited by the approval of penpulimab-kcqx's approval in the US FDA for first line and later line NPC," said Yu Xia, founder, chairwoman, president, CEO, Akeso, in the press release "Beyond reaching our first international regulatory milestone, this approval also provides an important immunotherapy treatment option for patients with NPC in the United States. The FDA approval of penpulimab-kcqx not only highlights the quality of our innovation but also underscores Akeso's focus on delivering treatments for difficult to treat cancers for patients around the world. We are deeply grateful to all the researchers, participants, and patients who have contributed to this success. Akeso will continue to advance first and best in class therapies, including bispecific antibodies and CD47 inhibitors, challenge global standards of care and unlocking the full potential of our pipeline for cancer patients everywhere."

The approval was based on results from the randomized, double-blind, international Phase III AK105-304 trial and the pivotal AK105-202 study, both of which supported the Biologics License Applications for the treatment. Full data are expected to be presented at the 2025 American Association for Cancer Research Annual Meeting. The FDA had previously granted penpulimab-kcqx with Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation.1

"This milestone enhances international treatment guidelines for advanced NPC and extends the benefits of China's innovations to global patients, ultimately reshaping the treatment landscape for metastatic NPC worldwide," said Chaosu Hu, principal investigator of penpulimab-kcqx, professor, Fudan University Shanghai Cancer Center, in the press release.

Earlier this week, Akeso also announced that its combination of ivonescimab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival. The results, from the Phase III HARMONi-6 trial, showed superiority over tislelizumab plus chemotherapy as a first-line treatment for advanced squamous non-small cell lung cancer.2

According to the American Cancer Society, there is fewer than one case of NPC per 100,000 people in most parts of the world, including the United States. However, the disease is significantly more common in regions such as South Asia, the Middle East, and North Africa. In certain areas of China, incidence rates reach 25 to 30 cases per 100,000 men and 15 to 20 cases per 100,000 women.

While the risk of developing NPC increases with age, cases can occur in childhood. In high-risk regions, the disease is most common among individuals aged 45 to 59 years. In lower-risk areas, it appears more frequently among those aged 15 to 24 years, then declines before peaking again between 65 and 79 years of age. Notably, men are two to three times more likely to be diagnosed with NPC than women.3

"The FDA approval of penpulimab-kcqx confirms its high efficacy and low toxicity, positioning China's innovative drug development in alignment with international standards," said Xiaozhong Chen, investigator of penpulimab-kcq, in the press release.

References

1. Akeso Announces FDA Approval for Penpulimab-kcqx in Two BLA Indications for Comprehensive Treatment of Advanced Nasopharyngeal Carcinoma. PR Newswire. April 24, 2025. Accessed April 25, 2025. Https://prnmedia.Prnewswire.Com/news-releases/akeso-announces-fda-approval-for-penpulimab-kcqx-in-two-bla-indications-for-comprehensive-treatment-of-advanced-nasopharyngeal-carcinoma-302437965.Html

2. Akeso's PD-1/VEGF Bispecific Antibody Demonstrates Meaningful Progression-Free Survival Benefits in Advanced Squamous NSCLC. PharmExec. April 23, 2025. Accessed April 25, 2025. Https://www.Pharmexec.Com/view/akeso-pd-1-vegf-bispecific-antibody-demonstrates-meaningful-progression-free-survival-benefits-advanced-squamous-nsclc

3. Key Statistics for Nasopharyngeal Cancer. American Cancer Society. Accessed April 25, 2025. Https://www.Cancer.Org/cancer/types/nasopharyngeal-cancer/about/key-statistics.Html

Akeso PD-1 Inhibitor Cleared As Keytruda Challenger Advances

News

Dr Yu Xia, founder, chairwoman, president and chief executive of Akeso

Hong Kong's Akeso has ended the week on a high note, with an FDA approval for its PD-1 inhibitor penpulimab and more data on PD-1/VEGF bispecific antibody ivonescimab.

Penpulimab has picked up a pair of approvals in nasopharyngeal carcinoma (NPC), becoming only the second drug to be cleared for treating the fairly rare form of head and neck cancer after Shanghai Junshi Biosciences' PD-1 inhibitor Loqtorzi (toripalimab), which reached the US market last year.

Akeso's antibody can be used as a monotherapy for adults with metastatic non-keratinising NPC with disease progression on or after platinum-based chemotherapy, after at least one other prior therapy, and in combination with chemotherapy (cisplatin or carboplatin and gemcitabine) for first-line treatment of recurrent or metastatic non-keratinising NPC.

It is the first approval for one of Akeso's internal pipeline of biologic drugs, although, penpulimab is already approved in China for similar NPC indications.

NPC is relatively rare in Western populations, but more common in Asia, and in most cases is associated with Epstein-Barr virus (EBV) infection. Keratinising forms of the cancer are thought to have a different pathology and are more common in the US than non-keratinising NPC.

"Beyond reaching our first international regulatory milestone, this approval also provides an important immunotherapy treatment option for patients with NPC in the US," said the company's president and chief executive, Dr Yu Xia.

The penpulimab approval came right on the heels of Akeso reporting new data with Summit Pharma-partnered ivonescimab, a drug that has already attracted considerable attention after besting MSD's best-selling PD-1 inhibitor Keytruda (pembrolizumab) in the HARMONi-2 trial in previously untreated, PD-L1-positive squamous and non-squamous non-small cell lung cancer (NSCLC).

Ivonescimab is already approved in China to treat EGFR inhibitor-resistant, advanced non-squamous NSCLC.

The new results from the HARMONi-6 trial come from a comparison of the PD-1/VEGF bispecific antibody in combination with chemo with BeiGene's PD-1 inhibitor Tevimbra (tislelizumab) plus chemo in squamous NSCLC and show that Akeso's drug "decisively beat" the rival regimen.

Details are scant at the moment but, according to Akeso, the results showed a "statistically significant and clinically meaningful" improvement with ivonescimab on the main endpoint of progression-free survival (PFS) in both PD-L1-positive and PD-L1-negative NSCLC.

The result "further positions ivonescimab to improve upon and replace the current standard of care for the treatment of NSCLC," said the company, while Dr Xia said it " demonstrated [ivonescimab's] breakthrough clinical value and market competitiveness as a next-generation cancer therapy."

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