FDA Approves Penpulimab-Kcqz for Indications in Nonkeratinizing Nasopharyngeal Carcinoma

The FDA approved penpulimab-kcqz (formerly AK105; Akeso Biopharma Co., Ltd.) for different indications within nonkeratinizing nasopharyngeal carcinoma (NPC). Penpulimab can be used with cisplatin (Platinol; Bristol Myers Squibb) or carboplatin (Paraplatin; Bristol-Myers Squibb) and gemcitabine (Gemzar; Eli Lilly and Company) for the first-line treatment of adults with recurrent or metastatic nonkeratinizing NPC, and as a single agent for adults with metastatic nonkeratinizing NPC who have disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy.¹ The approval follows results from the AK105-304 (NCT04974398) and AK105-202 (NCT03866967) clinical trials.^1-3

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The efficacy of penpulimab with cisplatin or carboplatin and gemcitabine was evaluated in the randomized, double-blind, multicenter phase 3 clinical trial AK105-304 (NCT04974398), which enrolled 291 patients with recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomly assigned to receive either penpulimab with cisplatin or carboplatin and gemcitabine followed by penpulimab or placebo with cisplatin or carboplatin and gemcitabine followed by placebo.^1,2

The primary efficacy outcome measure for this trial was progression-free survival (PFS), as assessed by a Blinded Independent Review Committee according to RECIST v1.1. Overall survival (OS) was a key secondary end point. The investigators observed a median PFS of about 9.6 months (95% CI: 7.1, 12.5) and 7.0 months (95% CI: 6.9, 7.3) in the penpulimab and placebo arms, respectively (HR: 0.45 [95% CI: 0.33, 0.62]; 2-sided p-value < .0001). Additionally, approximately 31% and 11% of patients were alive and progression-free after 12 months of follow-up in the penpulimab and placebo arms, respectively. At the time of this analysis, OS results were considered immature, with about 70% of pre-specified deaths for the final analysis reported, no detrimental trend was observed.^1,2

Further, the efficacy of single-agent penpulimab was evaluated in the open-label, multicenter, single-arm, single-country phase 3 trial, AK105-202 (NCT03866967). The trial enrolled 125 patients with unresectable or metastatic nonkeratinizing NPC who had disease progression after platinum-based chemotherapy and received at least 1 other line of therapy. Patients received penpulimab until disease progression or unacceptable toxicity, for a maximum of 24 months.^1,3

The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), according to RECIST v1.1 as assessed by an Independent Radiology Review Committee. The results indicated an ORR of about 28% (95% CI: 20, 37), but median DOR was not reached (95% CI: 9.2, not estimable).^1,3

Immune-mediated adverse events (AEs) in patients receiving penpulimab included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin AEs. The most common for penpulimab with cisplatin or carboplatin and gemcitabine were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia, and single-agent penpulimab were hypothyroidism and musculoskeletal pain. Further, fatal AEs occurred in about 1% of patients and included a case each of pneumonitis, septic shock, colitis, and hepatitis.¹

The recommended dose of penpulimab when used with cisplatin or carboplatin and gemcitabine is 200 mg every 3 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months, according to the FDA. Additionally, the recommended single-agent dose of penpulimab for previously treated NPC is 200 mg every 2 weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.¹

REFERENCES

1. US Food & Drug Administration. FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. News release. April 23, 2025. Accessed April 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma

2. A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma. ClinicalTrials.gov identifier: NCT04974398. Updated April 13, 2025. Accessed April 24, 2025. https://clinicaltrials.gov/study/NCT04974398

3. A Study of Anti-PD-1 AK105 in Patients With Metastatic Nasopharyngeal Carcinoma. ClinicalTrials.gov identifier: NCT03866967. Updated February 27, 2025. Accessed April 24, 2025. https://clinicaltrials.gov/study/NCT03866967