Irinotecan Liposome Combined with S-1 in PD-1/L1 Inhibitor Refractory Recurrent or Metastatic NPC

The Efficacy and Safety of Irinotecan Liposome Combined with S-1 in PD-1/L1 Inhibitor Refractory Recurrent or Metastatic Nasopharyngeal Carcinoma: a Prospective, Single-arm Phase 2 Study

This is a prospective, single-arm Phase 2 study to evaluate the efficacy and safety of Irinotecan Liposome injection combined with S-1 in patients with recurrent (unable to local curative treatment) or metastatic NPC who failed at least first-line anti-PD-1/L1.

Study Overview

• Status: Recruiting
• Conditions: Recurrent or Metastatic Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Irinotecan liposome; Drug: S-1

Detailed Description

Fifty-six recurrent (unable to local curative treatment) or metastatic NPC patients who had failed at least first-line anti-PD-1/L1, whether or not combined with chemotherapy, were eligible to receive Irinotecan Liposome injection combined with S-1 for up to 6 cycles. All patients will be treated until disease progression as determined by the investigator based on RECIST 1.1 criteria, intolerable toxicity, subject withdrawal of informed consent, initiation of new antitumor therapy, loss of follow-up, death, or study completion, whichever occurs first. Regular visits and imaging examinations will be conducted to evaluate the efficacy and safety of the treatment regimen.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingyuan Chen, MD, PhD; Phone Number: 18124188280; Email: chmingy@mail.sysu.edu.cn
• Study Contact Backup: Name: Rui You, MD, PhD; Phone Number: 13580439820; Email: your5@mail.sysu.edu.cn

Study Locations

• China
  • Guangzhou
    • Zhuhai, Guangzhou, China, 519000
      • Recruiting
      • Fifth affiliated hosptial of Sun-yat Sen university
      • Contact: Mingyuan Chen, MD, PhD; Phone Number: 18124188280; Email: chmingy@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Willing to participate in the study, sign the informed consent form (ICF), and comply with study plan visits, treatment plans, laboratory tests, and other study procedures.

  2. Age ≥ 18 years. 3. Nasopharyngeal carcinoma confirmed by histopathology (differentiated or undifferentiated non-keratinous carcinoma).

  4. Recurrent or metastatic nasopharyngeal carcinoma that has failed at least first-line anti-PD-1/L1, whether or not combined with platinum-containing standard regimen (Anti PD-1/L1 exposure at least 6 weeks, and the protocol used at the time of enrollment in this study meets one of the following two points: (1) Relapse during adjuvant therapy after radiotherapy, or relapse within 6 months after the end of treatment; (2) First-line treatment phase, progression during anti-PD-1/L1 treatment, or progression within 3 months after the end of anti-PD-1/L1).

  5. Recurrent or metastatic nasopharyngeal carcinoma that is unable to local curative treatment (surgery or radiotherapy).

  6. At least one measurable lesion according to RECIST 1.1 criteria (the spiral CT scan diameter of the measurable lesion is ≥ 10 mm or the short diameter of the enlarged lymph node is ≥15mm ); lesions that have undergone local treatment can be selected as target lesions if there is clear evidence of significant progress compared to the end of treatment.

  7. ECOG PS (Eastern Cooperative Oncology Group Performance Status) score 0-1. Expected survival ≥3 months.

  8. Adequate main organ function: a. Liver function: AST and ALT ≤ 2.5 times ULN, bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert disease and serum bilirubin level ≤ 3 times ULN could be enrolled; patients with liver metastasis, ≤ 5 times ULN); b. Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 30 mL/min according to Cockcroft-Gault formula; c. Hematology: neutrophil absolute value (ANC) ≥1.0×10^9/L, hemoglobin (Hb) ≥ 9.0 g/dL, platelets ≥ 100×10^9/L.

Exclusion Criteria:

• 1. Severe allergy to Irinotecan liposome (such as systemic rash/erythema hypotension, bronchospasm, angioedema, or anaphylaxis).

  2.CYP3A4 strong inducer used within 2 weeks, or CYP3A4/UGT1A1 strong suppressor used within 1 week prior to initial administration.

  3. Estimated survival < 3 months. 4.HBsAg positive and HBV DNA copy number positive (quantitative detection ≥2000 IU/ml); Chronic hepatitis C blood screening positive (HCV antibody positive). Patients with normal liver function and concurrent antiviral therapy were determined by the investigator to be eligible for enrollment.

  5. HIV-positive people. 6. Patients with active bacterial infection, fungal infection, viral infection, or interstitial pneumonia require systemic treatment within 1 week prior to first administration.

  7. Received chemotherapy, targeted therapy, immunotherapy, or any investigational drug or other antitumor therapy within 4 weeks or 5 half-lives before first administration (whichever is shorter but at least 2 weeks).

  8. Received Chinese medicine with antitumor activity within 14 days before administration; Received other investigational drugs within 4 weeks prior to initial dosing.

  9. Patients who had undergone major surgery within 3 months prior to initial dosing or planned to undergo major surgery during the study period.

  10. Severe embolic events, such as cerebrovascular accidents (including transient ischemic attacks) and pulmonary embolism, occurred in the 6 months before screening.

  11. Diagnosed and/or treated with other malignancies within 2 years before initial administration (except for curable malignancies that have undergone radical treatment, such as skin basal cell, carcinoma in situ of the cervix, papillary thyroid cancer, etc).

  12. Severe cardiovascular disease during the 6 months before enrollment, including but not limited to the following: Acute myocardial infarction, unstable angina pectoris, coronary angioplasty or stenting, deep vein thrombosis, stroke; New York Heart Association Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%; According to the investigator's assessment, clinically significant abnormal electrocardiogram (ECG) at the time of screening.

  13. Pregnant or lactating women. 14. Serious dysfunction of heart, lung, liver, kidney, and other vital organs; serious and/or uncontrollable disease that may affect the patient's participation in the study (including, but not limited to, uncontrolled diabetes, life-threatening autoimmune and bleeding disorders, substance abuse, neurological disorders, etc.).

  15. Other situations that the investigator determines to be inappropriate for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan liposome group; Irinotecan liposome injection combined with S-1 every 4 weeks for up to 6 cycles, until intolerable toxicity, subject withdrawal of informed consent, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.	Drug: Irinotecan liposome; Irinotecan liposome injection, 50mg/m2, D1、D15, ivgtt, Q4w.; Drug: S-1; S-1, D1-D14, BID, p.o., Q4w (BSA < 1.25 m2, 40 mg/dose; 1.25 m2 ⩽ BSA < 1.5 m2, 50 mg/dose; BSA ⩾ 1.5 m2, 60mg/dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) is defined as the proportion of patients with a complete response or partial response to treatment	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	NCI-CTCAE 5.0 standard is adopted.	1 year
Progression-free survival (PFS)	Progression-Free Survival PFS is defined as the duration from the date of treatment to progression or death	Through study completion, an average of 1 year
Overall survival (OS)	Overall survival (OS) is defined as the duration from the date of treatment to death or last follow-up, with no restriction on the cause of death.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Recurrence; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Irinotecan
• Other Study ID Numbers: ZDWY.BYAFZZX.031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No