NCT07070479

Combination Therapy for PD-1 Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma: A Bayesian Adaptive Phase II Trial

A Bayesian Adaptive Phase II Randomized Trial Comparing Ivonescimab, Ivonescimab Plus Nimotuzumab, Liposomal Mitoxantrone Plus Anti-PD-1 Antibody, and Liposomal Irinotecan Plus S-1 in Patients With PD-1-Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 208 (estimated)
• Sponsor: Ming-Yuan Chen · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, Bayesian adaptive, phase II clinical trial designed to evaluate the safety and efficacy of four treatment regimens in patients with recurrent (unamenable to local therapy) or metastatic nasopharyngeal carcinoma (NPC) who have failed after at least one prior platinum-containing standard regimen and anti-PD-1/PD-L1 therapy. The four treatment arms include: 1. Ivonescimab monotherapy, 2. Ivonescimab combined with nimotuzumab, 3. Liposomal mitoxantrone plus anti-PD-1 antibody, and 4. Liposomal irinotecan plus S-1.

Detailed description

Patients with recurrent (not amenable to local therapy) or metastatic nasopharyngeal carcinoma (NPC) who have progressed after at least one prior platinum-containing standard regimen and anti-PD-1/PD-L1 therapy are eligible for this study. This trial adopts a Bayesian Adaptive Randomization with Constant Power parameter (BARCP) design. The planned maximum sample size is 208 patients, with a minimum of 32 patients to be enrolled before potential early termination for futility or efficacy based on interim analysis. The first 40 patients will be randomized with equal probability to one of the four treatment arms: 1. Ivonescimab monotherapy 2. Ivonescimab combined with nimotuzumab 3. Liposomal mitoxantrone plus an anti-PD-1 antibody 4. Liposomal irinotecan plus S-1 Subsequent randomization probabilities will be updated based on objective response rate (ORR) using interim analyses, which will include decisions for early efficacy, futility, or reassignment of allocation probabilities for future participants. Interim analyses will be conducted every time 16 new patients complete ORR assessment. The minimum allocation probability for each treatment arm is constrained to 5%. All patients will receive treatment until disease progression (as determined by the investigator based on RECIST 1.1 criteria), intolerable toxicity, withdrawal of informed consent, initiation of new anticancer therapy, loss to follow-up, death, or study completion-whichever occurs first. Regular visits and imaging assessments will be conducted to evaluate the efficacy and safety of the treatment regimens.

Conditions

• Recurrent or Metastatic Nasopharyngeal Carcinoma

Interventions

Type	Name	Description
DRUG	Ivonescimab	Ivonescimab 10 mg/kg via intravenous infusion, until the occurrence of intolerable toxicity, withdrawal of informed consent, initiation of new antitumor therapy, loss to follow-up, or death, whichever occurs first.
DRUG	Nimotuzumab	Nimotuzumab 400 mg via intravenous infusion, Q3W, until the occurrence of intolerable toxicity, withdrawal of informed consent, initiation of new antitumor therapy, loss to follow-up, or death, whichever occurs first.
DRUG	Irinotecan liposome	Irinotecan liposome 50mg/m2 via intravenous infusion, D1, D15, Q4W for up to 6 cycles or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.
DRUG	S-1	S-1, D1-D14, BID, p.o., (BSA \< 1.25 m2, 40 mg/dose; 1.25 m2 ⩽ BSA \< 1.5 m2, 50 mg/dose; BSA ⩾ 1.5 m2, 60mg/dose), Q4W for up to 6 cycles or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.
DRUG	Mitoxantrone Hydrochloride Liposome	Mitoxantrone hydrochloride liposome 20mg/m2 via intravenous infusion, Q3W for up to 8 cycles or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first
DRUG	PD-1 Inhibitors	PD-1 blockade (comprising tislelizumab \<200 mg/cycle\>, carrellimab \<200 mg/cycle\>, or toripalimab \<240 mg/cycle\>) , Q3W for two years, or until intolerable toxicity, subject withdrawal of informed consent, diseases progression, initiation of new antitumor therapy, loss of follow-up, or death, whichever occurs first.

Timeline

• Start date: 2025-06-24
• Primary completion: 2027-01-30
• Completion: 2028-01-30
• First posted: 2025-07-17
• Last updated: 2025-09-18

Locations

6 sites across 1 country: China