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Peramprizumab kombinert med fastlege ± Anlotinib som neoadjuvant terapi ved lokoregionalt avansert nasofaryngeal karsinom

28. september 2026 oppdatert av: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Penpulimab Combined With GP ± Arotinib Induction Therapy + Concurrent Chemoradiotherapy + Adjuvant Penpulimab in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Clinical Trial

The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and Penpulimab ± Anlotinib in neoadjuvant therapy combined with Penpulimab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Radiotherapy combined with chemotherapy is the standard treatment method for locally advanced NPC. In the 2020 National Comprehensive Cancer Network (NCCN) guidelines, GP regimen induction chemotherapy combined with concurrent chemoradiotherapy has been established as evidence-based grade 2A.

Based on the results of phase 3 clinical trials, the addition of PD-1 monoclonal antibody to GP chemotherapy as a first-line treatment for patients with recurrent or metastatic nonkeratinizing NPC provided superior PFS, ORR and DoR than GP alone while maintaining a manageable safety profile. Therefore, the combination of PD-1 monoclonal antibody in GP induction chemotherapy may further improve the prognosis of patients with locally advanced NPC.

There is a complex interaction between tumor immune microenvironment and tumor vascular remodeling. Anti-PD-1 monoclonal antibody combined with anti-VEGF have synergistic effect and inhibit tumor growth.

Penpulimab is a new type of PD-1 monoclonal antibody. It has the characteristics of strong antigen binding and slow dissociation rate, which can maintain the antitumor activity of T cells.

Anlotinib is a multi-target tyrosine kinase inhibitor (TKI). It can effectively inhibit a variety of receptors, including vascular endothelial growth factor receptor (VEGFR), and block tumor angiogenesis more comprehensively.

Based on the above research background, this study adopts a two-stage design:

Stage I (Pick the Winner Study): For patients with locally advanced NPC, the complete response rate (CR) of tumor after induction chemotherapy was compared between the two groups of patients receiving GP + Penpulimab and GP + Penpulimab + arotinib before radiotherapy. The regimen with higher CR rate was the winner at this stage.

Stage II ( Cohort Expansion Study): The 3-year failure free survival (FFS) of patients in the winning regimen of expansion cohort was calculated through long-term follow-up and compared with the data in previous trials.

Studietype

Intervensjonell

Registrering (Faktiske)

105

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Kina
    • Guangdong
      • Guangzhou, Guangdong, Kina, 510060
        • Hai Qiang Mai

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 65 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Voluntary participation with Written informed consent.
  2. Age ≥ 18 years and ≤ 65 years, male or non-pregnant female.
  3. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
  4. Original clinical staged as III-IVa (according to the 8th AJCC edition),exclude T3-4N0, T3N1(Only retropharyngeal lymph nodes metastasized), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  5. White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
  7. Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.

Exclusion Criteria:

  1. Patients with recurrent or metastatic nasopharyngeal carcinoma.
  2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
  3. Prior therapy with Systemic chemotherapy.
  4. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
  5. Seropositivity for human immunodeficiency virus (HIV).
  6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
  7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
  8. Patients with immunodeficiency disease or a history of organ transplantation.
  9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
  10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
  11. Patients with severe, uncontrolled disease or infections.
  12. Received other research drugs or in other clinical trials at the same time.
  13. Refuse or fail to sign the informed consent .
  14. Patients with other treatment contraindications.
  15. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.
  16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml.
  17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: GP combine with Penpulimab and anlotinib neoadjuvant therapy+CCRT+Penpulimab adjuvant therapy

Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), penpulimab (200mg, day1), and anlotinib (10mg days 1-14) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with penpulimab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
Legemiddel: GP+Penpulimab+Anlotinib

GP combine with penpulimab and anlotinib neoadjuvant therapy+CCRT+penpulimab adjuvant therapy

Andre navn:
  • GP+AK105+AL3818
Aktiv komparator: GP combine with Penpulimab neoadjuvant therapy+CCRT+Penpulimab adjuvant therapy

Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on days 1,8) , cisplatin (80mg per square meter on day 1), penpulimab (200mg, day1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT) ,then followed by adjuvant therapy with penpulimab (200mg) every three weeks for a maximum of nine cycles after radiotherapy.
Legemiddel: GP+Penpulimab

GP combine with penpulimab neoadjuvant therapy+CCRT+penpulimab adjuvant therapy

Andre navn:
  • GP+AK105

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Stage 1(Pick the Winner Study): Complete Response
Tidsramme: 9 weeks

The proportion of patients who had a complete response was defined as those with all pathological cervical lymph nodes being less than 10 mm in the short axis and no unequivocal soft tissue mass in the local region. Disease response was evaluatedby by the Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) 95% confidence intervals (CIs) were calculated using the Clopper Pearson method
9 weeks
Stage 2 (Cohort Expansion Study): Failure-free survival (FFS)
Tidsramme: 3 years

Defined as the time from registration to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
3 years

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall survival (OS)
Tidsramme: 3 years

Defined as the time from registration to death from any cause or censored at the date of last follow-up.
3 years
Locoregional failure-free survival (LRRFS)
Tidsramme: 3 years

Defined as the time from registration to local or regional relapse, or death from any cause.
3 years
Distant metastasis-free survival (DMFS)
Tidsramme: 3 years

Defined as the time from registration to distant metastasis, or death from any cause.
3 years
Incidence rate of adverse events (AEs)
Tidsramme: 3 years

Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.
3 years
Objective Response Rate (ORR)
Tidsramme: 9 weeks

Objective response rate (ORR) was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.
9 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Sun Yat-sen University

Etterforskere

  • Hovedetterforsker: Hai-Qiang Mai, Ph.D, Sun Yat-Sen University Cancer Center

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

17. august 2022

Primær fullføring (Antatt)

1. oktober 2026

Studiet fullført (Antatt)

1. oktober 2028

Datoer for studieregistrering

Først innsendt

11. januar 2022

Først innsendt som oppfylte QC-kriteriene

14. januar 2022

Først lagt ut (Faktiske)

18. januar 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

2. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

28. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 2021-FXY-504

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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