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

NCT07070479 | Recruiting Phase 2 DMC

• 1 other identifier: ZDWY.BYAFZZX.034
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 6

Brief 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. 1.Ivonescimab monotherapy,
2. 2.Ivonescimab combined with nimotuzumab,
3. 3.Liposomal mitoxantrone plus anti-PD-1 antibody, and
4. 4.Liposomal irinotecan plus S-1.

Conditions

Recurrent or Metastatic Nasopharyngeal Carcinoma

Keywords

nasopharyngeal carcinoma; Recurrent; metastatic; PD-1 resistance; Bayesian adaptive design; Ivonescimab; Nimotuzumab; Liposomal mitoxantrone; Liposomal irinotecan; S-1

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Defined as the proportion of patients whose tumors shrink to complete response (CR) or partial response (PR) and remain for a certain period of time according to RECIST 1.1

  1 year

Secondary Outcomes (7)

• Progression-free Survival (PFS)

  1 year

• Overall Survival (OS)

  1 year

• Duration of Response (DOR)

  1 year

• Disease Control Rate (DCR)

  1 year

• Adverse Events Reporting

  1 year

Study Arms (4)

Ivonescimab Monotherapy

EXPERIMENTAL

Participants will receive Ivonescimab at a dose of 10 mg/kg via intravenous infusion, Q3W. Treatment will continue 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: Ivonescimab

Ivonescimab plus Nimotuzumab

EXPERIMENTAL

Participants will receive Ivonescimab at a dose of 10 mg/kg via intravenous infusion, combined with Nimotuzumab 400 mg via intravenous infusion, Q3W. Treatment will continue 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: Ivonescimab; Drug: Nimotuzumab

Mitoxantrone Plus PD-1 Inhibitor

EXPERIMENTAL

Participants will receive mitoxantrone hydrochloride liposome at 20 mg/m² via intravenous infusion, combined with a PD-1 inhibitor - either tislelizumab (200 mg/cycle), camrelizumab (200 mg/cycle), or toripalimab (240 mg/cycle) - Q3W, for up to 8 cycles. After combination therapy, participants will continue receiving PD-1 blockade monotherapy every 3 weeks for up to 2 years, or 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: Mitoxantrone Hydrochloride Liposome; Drug: PD-1 Inhibitors

Irinotecan plus S-1

EXPERIMENTAL

Participants will receive liposomal irinotecan at 50 mg/m² via intravenous infusion on D1 and D15, Q4W, in combination with oral S-1 administered BID on D 1-14 of each cycle, for up to 6 cycles. The dose of S-1 is based on body surface area (BSA). BSA \< 1.25 m²: 40 mg per dose ; 1.25 m² ≤ BSA \< 1.5 m²: 50 mg per dose; BSA ≥ 1.5 m²: 60 mg per dose Treatment will continue 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; Drug: S-1

Interventions

Ivonescimab DRUG

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.

Ivonescimab Monotherapy; Ivonescimab plus Nimotuzumab

Nimotuzumab DRUG

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.

Ivonescimab plus Nimotuzumab

Irinotecan liposome DRUG

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.

Irinotecan plus S-1

S-1 DRUG

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.

Irinotecan plus S-1

Mitoxantrone Hydrochloride Liposome DRUG

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

Mitoxantrone Plus PD-1 Inhibitor

PD-1 Inhibitors DRUG

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.

Mitoxantrone Plus PD-1 Inhibitor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (either differentiated or undifferentiated subtype, corresponding to WHO type II or III).
• Age between 18 and 70 years.
• Performance Status (PS) score of 0 or 1.
• Disease progression after prior platinum-based doublet chemotherapy.
• Received at least one line of systemic therapy previously. (Progression occurring during or within 6 months after definitive concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy, or treatment completion may be counted as first-line treatment.)
• Resistance to anti-PD-1 antibody therapy (either combination or sequential), including primary or secondary resistance（PD-1 exposure must be at least 6 weeks.）
• At least one measurable lesion according to RECIST 1.1 criteria.
• Adequate organ function:
• Hematology: WBC ≥ 4000/μL, absolute neutrophil count ≥ 2000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL.
• Liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome and bilirubin ≤ 3 × ULN are eligible); AST and ALT ≤ 3 × ULN; alkaline phosphatase ≤ 3 × ULN; albumin ≥ 3 g/dL.
• Coagulation: INR, prothrombin time (PT), or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min calculated by Cockcroft-Gault formula. Proteinuria: Urine protein/creatinine ratio (UPC) \< 1.0. For UPC ≤ 0.5, no further testing is required; for UPC \> 0.5, 24-hour urine protein must be \< 1000 mg for eligibility.
• Estimated life expectancy of at least 3 months.
• Signed informed consent and willingness and ability to comply with study visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Locoregional recurrent lesions that are amenable to definitive (curative) treatment, such as surgery.
• Prior treatment with any regimen included in the study protocol.
• Prior use of agents targeting the VEGF or VEGFR pathway.
• Diagnosis and/or treatment of another malignancy within the past 5 years, with the exception of adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ.
• Receipt of surgery, chemotherapy, radiotherapy, immunotherapy, any investigational agent, or other anti-cancer therapy within 4 weeks prior to enrollment (or within 2 weeks for palliative radiotherapy).
• Tumor encasement of the internal carotid artery or evidence of nasopharyngeal necrosis observed on endoscopy prior to enrollment.
• Active peptic ulcers or gastrointestinal surgery within 1 month prior to enrollment; history within 6 months of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal hemorrhage, esophageal varices, or pathological fracture.
• Severe infection requiring intravenous antibiotics, antifungals, or antivirals within 4 weeks prior to the first dose, or unexplained fever \>38.5°C within 7 days prior to the first dose; baseline WBC \>15 × 10⁹/L.
• Known hypersensitivity to study drugs or excipients, or a history of severe hypersensitivity reactions such as generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis.
• Conditions that may affect oral drug absorption, including dysphagia, nausea/vomiting, chronic diarrhea, or bowel obstruction.
• Ongoing treatment with immunosuppressants or systemic corticosteroids (\>10 mg/day prednisone or equivalent) within 2 weeks prior to the first dose.
• Presence of any active autoimmune disease or a history of autoimmune diseases likely to recur (including but not limited to interstitial pneumonitis, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism). Exceptions include vitiligo and childhood asthma now in complete remission. Patients with asthma requiring bronchodilator therapy are excluded.
• History of acute exacerbation of chronic obstructive pulmonary disease or other respiratory disease requiring hospitalization within 1 month prior to enrollment; patients with active tuberculosis or those who received anti-TB therapy within 1 year prior to screening.
• HIV positive; or positive HBsAg with quantifiable HBV DNA ≥1000 cps/mL; or positive anti-HCV antibody.
• Receipt of live vaccines within 4 weeks prior to first dose or anticipated during the study period.

Sponsors & Collaborators

• Ming-Yuan Chen: lead

Study Sites (6)

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

NOT YET RECRUITING

Zhongshan People's Hospital

Zhongshan, Guangdong, China

NOT YET RECRUITING

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

RECRUITING

Xiangya Hospital, Central South University

Changsha, Hunan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Recurrence; Nasopharyngeal Carcinoma; Neoplasm Metastasis

Interventions

nimotuzumab; irinotecan sucrosofate; S 1 (combination); Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Mingyuan Chen

CONTACT

+86 18124188280; chmingy@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professior, Chief physician

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 17, 2025
• Study Start: June 24, 2025
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2028
• Last Updated: September 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)