Evaluating Ivonescimab in PD-1 Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma

NCT07565389 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-1970
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed as a single-arm, open-label, phase II trial to evaluate the efficacy and safety of ivonescimab in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) who have progressed on prior an immune checkpoint inhibitor and platinum-based chemotherapy.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

Ivonescimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR), defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) as assessed by investigator review using iRECIST

  Best response at 1 year

Secondary Outcomes (8)

• Progression-Free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

• Duration of Response (DoR)

  3 years

• Disease Control Rate (DCR)

  3 years

• Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs)

  from enrolment till 3 months after end of treatment

Study Arms (1)

Cohort A & B

EXPERIMENTAL

We plan to enrol 32 patients with R/M NPC and who had failed prior platinum-based chemotherapy and anti-PD1 therapy in this study from (Cohort A) and we will have an additional cohort B consisting of 10 patients with R/M NPC and who had failed prior platinum-based chemotherapy, PD1-inhibitor and anti-angiogenic therapy.

Drug: Ivonescimab 20 mg/kg

Interventions

Ivonescimab 20 mg/kg DRUG

Subjects will receive intravenous ivonescimab at a dose of 20 mg/kg administered every 3 weeks until disease progression, intolerable toxicities, or withdrawal from the study.

Cohort A & B

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is eligible to be included in the study only if all the following criteria are met:
• The participant (or legally acceptable representative if applicable) provides written consent for the trial.
• Participant is at least 21 years of age on the day of signing informed consent
• Has a locally or centrally determined histologically or cytologically confirmed diagnosis of Epstein Barr Virus (EBV)-positive nasopharyngeal carcinoma Note: The EBV status is to be determined by the EBV-encoded small RNA in situ hybridization (EBER in situ hybridization \[ISH\]) assay. If EBV-positive status has been previously determined by EBER ISH assay, then no re-testing is required. If EBV status by EBER ISH assay has not been previously determined, tumour tissue from archival tissue may be submitted for EBV determination.
• Has recurrent or metastatic (R/M) disease not amenable to curative local therapy (surgery or radiation)
• Must have seen at least 1 prior line of systemic treatment and has progressed on prior platinum-based chemotherapy and anti-PD1 therapy in the R/M setting OR Progressed within 6 months of previous multimodal therapy containing platinum-based chemotherapy and anti-PD1 therapy in the locally advanced setting.
• Has measurable disease based on iRECIST.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has an adequate organ function as defined in the following table (table 1). Specimens must be collected within 10 days prior to the start of study treatment
• Willing to provide blood and tumour tissue samples (newly obtained biopsy if clinically feasible or archival specimen) to support exploratory biomarker analysis.

You may not qualify if:

• Participant is excluded from the study if ANY of the following criteria apply:
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment.
• Has prior anti-angiogenic therapy in the R/M setting or within 6 months as part of multimodality therapy in the locally advanced setting. \[Applies to cohort A only\]
• Has tumour that encases major arteries which in the opinion of the investigator carries high risk of vessel wall dehiscence.
• Has a condition requiring systemic steroid therapy (\> 10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
• Note: Inhaled or topical steroids and adrenal replacement doses \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted if \< or = 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has hypersensitivity to ivonescimab or any of its components.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast or cervical carcinoma in situ) that have undergone potentially curative therapy are not excluded.
• Has an active infection requiring systemic therapy, or serious non-healing wound, ulcer or bone fracture.
• Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of ≥ 3 anti-hypertensive drugs or systolic blood pressure greater than 150 mmHg).
• Recent cardiovascular thromboembolic event, such as the following:

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Cancer Institute, Singapore, National University Health System

Singapore, Singapore

Location

Related Publications (2)

• Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005 Jun 11-17;365(9476):2041-54. doi: 10.1016/S0140-6736(05)66698-6.

  PMID: 15950718 BACKGROUND

• Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.

  PMID: 25769204 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

• Wan Qin Chong

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wan Qin Chong

CONTACT

+65 69082222; wan_qin_chong@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is designed as a single-arm, open-label, phase II trial to evaluate the efficacy and safety of ivonescimab in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) who have progressed on prior an immune checkpoint inhibitor and platinum-based chemotherapy.

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: May 4, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: May 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: They will be available beginning 3 months after Article publication with no end date.
• Access Criteria: other researchers should submit requests for access to the patient-level data to the corresponding author, including a proposal outlining their reasons for required data. Following a signed data access agreement, the data will be made available by a link sent from the corresponding author to the requester.

Locations

SG (1)