Adebrelimab and Chemoradiotherapy in High-risk LANPC

Official title

Adebrelimab Combined with Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase 2, Multicenter, Single-arm Clinical Trial

Overview

This trial aims to study the role of Adebrelimab combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) for high-risk locoregionally advanced nasopharyngeal carcinoma(LANPC).

Detailed description

The trial plans to enroll patients with stage IVA+T3N2M0 (AJCC 8th) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Adebrelimab in induction chemotherapy and adjuvant chemotherapy. Adebrelimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 9 cycles in adjuvant therapy.

Interventions

• Drug Adebrelimab
  Drug: Adebrelimab Adebrelimab 1200mg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively. Other Names: PD-L1 antibody Drug: Gemcitabine Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation. Other Names: GEM Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 1

Primary outcome measures

• Failure-free survival (FFS) [Time frame: 3 years]

Secondary outcome measures (6)

• Overall survival (OS) [Time frame: 3 years]
• Distant metastasis-free survival (DMFS) [Time frame: 3 years]
• Locoregional recurrence-free survival (LRRFS) [Time frame: 3 years]
• Adverse events (AEs) and serious adverse events (SAEs) [Time frame: 3 years]
• Quality of life (QoL) [Time frame: 3 years]
• Failure-free survival (FFS) within different subgroups [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Patients with histologically confirmed nasopharyngeal carcinoma.
• Tumor staged as IVA+T3N2M0 (AJCC 8th).
• Eastern Cooperative Oncology Group performance status ≤1.
• Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
• Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
• Patients must be informed of the investigational nature of this study and give written informed consent.
• Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug

Exclusion criteria

• Age > 65 or < 18.
• Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml
• Hepatitis C virus (HCV) antibody positive
• Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
• Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
• Has a known history of interstitial lung disease.
• Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
• Is pregnant or breastfeeding.
• Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
• Has known allergy to large molecule protein products or any compound of Adebrelimab.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• The First Affiliated Hospital of Xiamen University — Xiamen
• Nanfang Hospital, Southern Medical University — Guangzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• West China Hospital, Sichuan University — Chengdu

Publications

• Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induct PMID 31150573
• Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomis PMID 35576956
• Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. PMID 28837405
• Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consorti PMID 29584545

Identifiers

NCT: NCT06349889 · MA-NPC-II-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗