28 Apr AACR: PFS Extended in Nasopharyngeal Carcinoma in Trial of anti-PD-1 Antibody Penpulimab Plus Chemotherapy
Dr. Shreenivas
MedicalResearch.com Interview with:
Aditya Shreenivas M.D., M.S.
Assistant Professor
Department of Medical Oncology & Therapeutics Research
City of Hope
https://www.cityofhope.rg/aditya-shreenivas
MedicalResearch.com: What is the background for this study?
Response: Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor of the head and neck region with a distinct geographical distribution, with incidence rates as high as 30 per 100,000 in endemic regions like Asia and North Africa but less than 1 per 100,000 worldwide. Despite comprehensive curative intent therapy, up to 30% of patients with advanced NPC experience treatment failure, primarily due to recurrence and/or metastasis. This high mortality rate highlighted the urgent need for effective treatments.
Clinical trials (JUPITER-02, CAPTAIN-1st, and RATIONALE-309) showed improved progression-free survival by adding anti-PD-1 antibodies to chemotherapy for first-line treatment of recurrent or metastatic NPC. However, these studies were conducted exclusively in Asian populations.
Penpulimab is a humanized anti-PD-1 antibody that’s unique because it is a IgG1 subtype with a modified Fc segment. This structure potentially improves efficacy and safety compared to other anti-PD-1 drugs through lower immune-related adverse events.
MedicalResearch.com: What are the main findings?
Response: This global, phase 3 trial showed that:
- Penpulimab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (9.63 months vs. 7.00 months; hazard ratio 0.45).
- The PFS benefit was consistent across all pre-specified subgroups, including patients with liver metastasis, different PD-L1 expression levels, and various EBV DNA levels.
- The safety profile was manageable, with similar grade ≥3 treatment-related adverse events between the penpulimab and placebo arms (89.0% vs. 85.9%). Grade ≥3 immune-related adverse events occurred in only 6 (4.1%) patients with penpulimab.
MedicalResearch.com: Are there recognized causes for nasopharyngeal carcinoma?
Response: Yes, the paper mentions several recognized causes for NPC. It states that the development of NPC is associated with an interplay between:
- Genetic susceptibility
- Environmental exposures
- Epstein-Barr virus (EBV) infections
The paper also notes differences in histological types between regions. The keratinizing squamous cell carcinoma is prevalent in lower incidence regions like North America and Europe, whereas the non-keratinizing squamous cell carcinoma is mostly found in regions with higher incidences like China and North Africa.
MedicalResearch.com: What should readers take away from your report?
Response: Readers should understand that:
- Penpulimab plus chemotherapy represents a promising new treatment option for patients with recurrent or metastatic NPC, significantly improving progression-free survival.
- The safety profile was manageable with relatively low incidence of severe immune-related adverse events compared to other PD-1 inhibitors.
- The benefit was consistent across various patient subgroups, suggesting broad applicability.
- This study expanded enrollment beyond Asian populations, though the number of non-Asian participants remained small.
- Penpulimab’s unique IgG1 structure with modified Fc segment potentially contributes to its efficacy and safety profile.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: What recommendations do you have for future research as a result of this study?
Based on the study, future research should focus on:
- Longer follow-up to confirm the overall survival benefit associated with penpulimab.
- Further investigation of biomarkers for patient selection, as the study showed PD-L1 expression level was not a clear prognostic marker for immunotherapy response in R/M NPC.
- Additional studies combining penpulimab with other novel therapies to confirm any potential advantages in efficacy or safety in different treatment settings.
Disclosures:
The study was supported by Akeso Biopharma, The trial is registered at ClinicalTrials.gov (NCT04974398).
My disclosures:
Advisory board member: Lilly, Taiho, Merus
Steering committee member: Bayer 22752 study
Research support: Foundation one
Citation: AACR Abstract April 27 2025
Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304)
https://www.abstractsonline.com/pp8/#!/20273/presentation/10398
More information:
- Zhang Y, Rumgay H, Li M, Cao S, Chen W. Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling. JMIR Public Health Surveill. 2023 Sep 20;9:e49968.
doi: 10.2196/49968. PMID: 37728964; PMCID: PMC10551785.
- Medscape (2025). X Post on Nasopharyngeal carcinoma and EBV
https://x.com/Medscape/status/1914454102307709373
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Last Updated on April 28, 2025 by Marie Benz MD FAAD
