Penpulimab Combined With GP ± Anlotinib as Neoadjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

NCT05193617 | Active Not Recruiting Phase 2

• 1 other identifier: 2021-FXY-504
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Stage 1(Pick the Winner Study): Complete Response

  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)

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

  3 years

Secondary Outcomes (5)

• Overall survival (OS)

  3 years

• Locoregional failure-free survival (LRRFS)

  3 years

• Distant metastasis-free survival (DMFS)

  3 years

• Incidence rate of adverse events (AEs)

  3 years

• Objective Response Rate (ORR)

  9 weeks

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: GP+Penpulimab+Anlotinib

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

ACTIVE COMPARATOR

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.

Drug: GP+Penpulimab

Interventions

GP+Penpulimab+Anlotinib DRUG

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

Also known as: GP+AK105+AL3818

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

GP+Penpulimab DRUG

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

Also known as: GP+AK105

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation with Written informed consent.
• Age ≥ 18 years and ≤ 65 years, male or non-pregnant female.
• Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
• 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.
• White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
• 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) .
• Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.

You may not qualify if:

• Patients with recurrent or metastatic nasopharyngeal carcinoma.
• Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
• Prior therapy with Systemic chemotherapy.
• Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
• Seropositivity for human immunodeficiency virus (HIV).
• Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
• Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
• Patients with immunodeficiency disease or a history of organ transplantation.
• Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
• Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
• Patients with severe, uncontrolled disease or infections.
• Received other research drugs or in other clinical trials at the same time.
• Refuse or fail to sign the informed consent .
• Patients with other treatment contraindications.
• Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Hai Qiang Mai

Guangzhou, Guangdong, 510060, China

Location

Related Publications (2)

• 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 Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

  PMID: 31150573 BACKGROUND

• Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.

  PMID: 34341578 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Hai-Qiang Mai, Ph.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 18, 2022
• Study Start: January 20, 2022
• Primary Completion: January 1, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)