FDA Oks Penpulimab for First-Line Non-Keratinizing Nasopharyngeal Carcinoma
The FDA has approved penpulimab with chemotherapy for first-line recurrent/metastatic non-keratinizing nasopharyngeal carcinoma and alone after prior treatment.
US FDA
- The FDA approved penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine as a first-line treatment for adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC).
- Penpulimab was also approved as a single agent for adult patients with metastatic non-keratinizing NPC who experienced disease progression after platinum-based chemotherapy and at least 1 other prior line of therapy.
- The approval of the combination therapy was based on data from the phase 3 Study AK105-304 (NCT04974398), and the single-agent approval was supported by findings from the phase 2 Study AK105-202 (NCT03866967).
The FDA has granted approval to the combination of penpulimab plus cisplatin or carboplatin and gemcitabine for the first-line treatment of adult patients with recurrent or metastatic non-keratinizing NPC.1 The FDA has also approved single-agent penpulimab for the treatment of adult patients with metastatic non-keratinizing NPC with disease progression on or post platinum-based chemotherapy and at least 1 other previous line of therapy.
The approval of the combination therapy was based on data from the phase 3 Study AK105-304, which showed a statistically significant improvement in median progression-free survival (PFS) of 9.6 months for the penpulimab plus chemotherapy arm compared with 7.0 months for the placebo plus chemotherapy arm (HR, 0.45; 95% CI, 0.33-0.62; 2-sided P <.0001).
The single-agent approval was supported by findings from the phase 2 Study AK105-202, which demonstrated an overall response rate (ORR) of 28% (95% CI, 20%-37%) with a median duration of response (DOR) that was not reached (95% CI, 9.2-not estimable).
Head and neck cancer: © steph photographies - stock.adobe.com
For safety, the most common adverse events (AEs) seen in at least 20% of patients given the combination regimen were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia. For those treated with single-agent penpulimab, the most common AEs included hypothyroidism and musculoskeletal pain. Moreover, AEs that led to death were reported in 1% of patients, including pneumonitis, septic shock, colitis, and hepatitis (n = 1 each).
The recommended dose for the combination therapy is 200 mg of penpulimab every 3 weeks, and for single-agent therapy, it is 200 mg every 2 weeks, in both cases until disease progression or unacceptable toxicity, with a maximum duration of 24 months.
Behind the 2 Trials Supporting Penpulimab’s Approval
Study AK105-304
Study AK105-304 was a randomized, double-blind, multicenter trial in patients with recurrent or metastatic NPC who had not received prior systemic chemotherapy for advanced disease.2 Enrollment was open to patients aged 18 to 75 with histologically or cytologically confirmed recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease.1,2
Patients were also required to have a life expectancy of at least 3 months, an ECOG performance status of 0 or 1, 1 or more measurable lesion per RECIST 1.1 criteria, and adequate organ function.2
Once enrolled, patients were randomized in a 1:1 fashion to receive the combination of penpulimab plus cisplatin or carboplatin and gemcitabine, followed by penpulimab alone, or placebo with cisplatin or carboplatin and gemcitabine, followed by placebo.
The primary end point of the study was PFS, and secondary end points were overall survival (OS), ORR, DOR, disease control rate, and safety.
Study AK105-202
Study AK105-202 was a multicenter, single-arm, open-label, phase 2 study in patients with unresectable or metastatic non-keratinizing NPC with disease progression after platinum-based chemotherapy and at least 1 other prior therapy.
Patients aged 18 to 75 years with histologically confirmed unresectable or metastatic non-keratinizing NPC who had disease progression after platinum-based chemotherapy and at least 1 other line of therapy were eligible for enrollment in the study.3 Patients also were required to have a life expectancy of 3 months or more, at least 1 measurable tumor lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.
Patients were treated with penpulimab, and treatment continued until disease progression or unacceptable toxicity for up to 24 months.1
The primary end point was ORR. Secondary end points consisted of PFS, DOR, DCR, OS, and safety.
