Integrating Allogeneic NK Cells in High-risk Advanced Stage III-IV Nasopharyngeal Cancer Patients (AlloNK1)

March 24, 2026 updated by: Singapore General Hospital

Phase 1/2 Trial Integrating Allogeneic NK Cells in High-risk Advanced Stage III-IV Nasopharyngeal Cancer Patients

This clinical trial aims to determine whether Natural Killer (NK) cell therapy administered in combination with concurrent chemoradiotherapy (CRT) can reduce recurrence in patients with advanced nasopharyngeal cancer (NPC), and to identify the highest safe and tolerable dose of allogeneic NK cells. Allogeneic NK cells, derived from healthy donors, have demonstrated good tolerability in cancer patients.

The primary research questions are:

  1. What is the maximum tolerated dose (MTD) of allogeneic NK cells when administered with CRT in NPC patients?
  2. Can the addition of allogeneic NK cells to standard CRT reduce the proportion of NPC patients with detectable plasma EBV-DNA from 30% to 10%?

Phase 1: Participants will receive one of five escalating doses of allogeneic NK cells with CRT to determine the MTD.

Phase 2: Participants will receive the established MTD NK dose together with CRT.

Participants will undergo regular safety monitoring, side-effect assessment, measurement of plasma EBV-DNA levels, and surveillance for disease recurrence.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigator plans to enrol 31 newly diagnosed NPC patients with Stage III-IVA/B (T1-4, N1-3, M0) disease who are scheduled to receive standard-of-care treatment over an estimated 24-36-month period.

The clinical trial consists of a Phase 1 dose-escalation study followed by a single-arm Phase 2 study. In Phase 1, at least six participants will be treated at the MTD of allogeneic NK cells, after which an additional 25 participants are expected to be enrolled in Phase 2.

Phase 1 will use the Bayesian Model Averaging Continual Reassessment Method (BMA-CRM) to determine the MTD, evaluating five NK-cell dose levels of 0.5×10⁷, 0.8×10⁷, 1.1×10⁷, 1.4×10⁷, and 1.8×10⁷ cells/kg, with the starting dose set at 0.8×10⁷ cells/kg. Dose-limiting toxicity (DLT) is defined as Grade 3 to 5 toxicities per CTCAE criteria, and the target toxicity limit (TTL) is set at a maximum allowable DLT probability of 30%. Toxicity probability will be reassessed whenever a DLT occurs to determine whether it exceeds the TTL. If the cohort completes evaluation at a given dose level and the toxicity probability is within the TTL, dose escalation will proceed; however, if the toxicity probability exceeds the TTL, the dose will be rejected, and de-escalation will occur. When toxicity probability is low, accelerated escalation may be implemented.

Phase 1 will conclude once six participants have been treated at the designated MTD without developing Grade 3 to 5 toxicities; at that point, the MTD will be accepted. All participants in Phase 1 will receive standard NPC treatment combined with the NK-cell dose evaluated at the time of their enrollment.

Phase 2 is a single-arm study based on historical findings that approximately 25% to 30% of locally advanced NPC patients continue to exhibit detectable circulating EBV-DNA following standard CRT. The study hypothesizes that the addition of allogeneic NK cells will reduce this proportion to 10%.

All participants in Phase 2 will receive standard CRT along with NK-cell infusions administered once weekly during weeks 3, 6, 7, 8, 9, and 10. Interleukin-2 (200 IU/mL) will be co-administered with NK cells in Plasma-Lyte 148 supplemented with 2% human serum albumin (HSA). The primary endpoint of Phase 2 is the reduction in the proportion of patients with detectable post-treatment circulating EBV-DNA. At week 9, if the participants' circulating EBV-DNA levels have decreased but remain detectable, would be given an option for an additional four NK-cell infusions during weeks 12 to 15.

The secondary endpoint is the improvement in survival and recurrence rates within 24 to 36 months compared with historical cohorts receiving standard treatment alone. NK cells will be generated from healthy-donor PBMCs.

Study Type

Interventional

Enrollment (Estimated)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosed with NPC Stage III-IVA/B (T1-4, N1-3, M0)
  • Able to tolerate convectional CRT
  • Detectable EBV level at diagnosis
  • Adequate organ function ANC ≥ 1500/µL Platelet count ≥ 100,000/µL Creatinine clearance ≥60ml/minute Total bilirubin ≤ 1.5 x upper limit normal (ULN) AST ≤ 2 x upper limit normal ALT ≤ 2 x upper limit normal
  • ECOG performance status of 0-1

Exclusion Criteria:

  • History of Autoimmune Disease or any condition resulting in immunocompromised state (e.g., Drug induced)
  • ECOG performance status above or equal to 2
  • Poor Organ Function
  • Lactating or pregnant
  • Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Concurrent and adjuvant allogeneic NK cell therapy

Participants will receive standard chemoradiotherapy for locally advanced nasopharyngeal carcinoma along with adjuvant therapy of NK cells. Nk cells would be enriched and expanded using PBMCs from healthy donors.

Phase 1 dose escalation study which uses 5 different dosages of 0.5 x 10^7, 0.8x10^7, 1.1x10^7, 1.4 x 10^7, and 1.8x10^7 to determine the Maximum tolerated dose (MTD). If the MTD is determined in phase 1, the study will enter phase 2, where the determined dose level will be used for participants. The participants will receive six intravenous NK cell infusions at weeks 3,6,7,8,9, and 10 during and after CRT. If the participant's EBV level is still detectable, they would be suggested for supplementary NK cell treatments for an additional four weeks.
Biological: Allogenic expanded Natural Killer Cells (AlloNK1)

The NK cells would be enriched and expanded ex vivo in a GMP facility from healthy donor PBMCs. Prior to administration, the NK cells would be formulated in an infusion medium based on the corresponding dose level that is required for each participant.

Participants will receive an intravenous infusion of NK cells during and after the standard CRT. Six doses are administered at weeks 3,6,7,8,9, and 10. In Phase 1, NK cell doses range from 0.5x10^7 to 1.8x10^7 cells/kg for the determination of the maximum tolerated dose (MTD). In phase 2, all participants will receive NK cells at the established MTD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the MTD of allogenic NK cells
Time Frame: From enrollment to the end of treatment at week 10
The primary objective of this trial is to determine the MTD of allogeneic NK cells when used with concurrent CRT in advanced NPC patients.
From enrollment to the end of treatment at week 10
The percentage of patients with detectable plasma EBV-DNA decreased to 10% post treatment
Time Frame: From day of enrollment to the end of treatment at week 10
Primary endpoint is set at the percentage of patients with detectable post-treatment circulating EBV-DNA has decreased from 30% to 10%.
From day of enrollment to the end of treatment at week 10

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the patient survival and recurrence rate post-treatment
Time Frame: 24 to 36 months after the last treatment done at week 10
Secondary endpoint is in determining the change in patient survival and recurrence rate within 24-36 months post-treatment under this new treatment regimen when compare with historic cohorts under standard treatments
24 to 36 months after the last treatment done at week 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Singapore General Hospital

Investigators

  • Principal Investigator: Lim Chwee Ming, Singapore General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 19, 2025

First Posted (Actual)

November 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-2264
  • CSAINV22jul-0014 (Other Grant/Funding Number: National Medical Research Council (NMRC))
  • CTGIIT23jul-0003 (Other Grant/Funding Number: National Medical Research Council (NMRC))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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