Nasopharyngeal Carcinoma (NPC)Phase 1/2AlloNK1NCT07247201
Integrating Allogeneic NK Cells in High-risk Advanced Stage III-IV Nasopharyngeal Cancer Patients
A Phase 1/2 study testing Allogenic expanded Natural Killer Cells (AlloNK1) in people with Nasopharyngeal Carcinoma (NPC) and Minimal Residual Disease, run by Singapore General Hospital at 1 site in Singapore.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Nasopharyngeal Carcinoma (NPC), Minimal Residual Disease, Recurrent Nasopharyngeal Carcinoma
- What is being tested?
- Allogenic expanded Natural Killer Cells (AlloNK1)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteSingapore
- Study dates
- Apr 2026to Sep 2026
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site
Singapore General Hospital
Singapore
Lim Chwee Ming, +65 63265978, lim.chwee.ming@singhealth.com.sg
About this study
Official title: 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:
Read more
- What is the maximum tolerated dose (MTD) of allogeneic NK cells when administered with CRT in NPC patients?
- 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.
Read the 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.
- Conditions
- Nasopharyngeal Carcinoma (NPC), Minimal Residual Disease, Recurrent Nasopharyngeal Carcinoma, Maximum Tolerated Dose
- Being tested
- Allogenic expanded Natural Killer Cells (AlloNK1)
- Keywords
- Advanced Nasopharyngeal Cancer, Epstein-Barr Virus DNA, Allogeneic NK Cells, Maximum Tolerated Dose
- Medical subject headings
- Nasopharyngeal Carcinoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic expanded Natural Killer Cells (AlloNK1)Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Concurrent and adjuvant allogeneic NK cell therapy | Experimental | 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. Receives: Biological: Allogenic expanded Natural Killer Cells (AlloNK1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the MTD of allogenic NK cells
The primary objective of this trial is to determine the MTD of allogeneic NK cells when used with concurrent CRT in advanced NPC patients.
Measured: From enrollment to the end of treatment at week 10
The percentage of patients with detectable plasma EBV-DNA decreased to 10% post treatment
Primary endpoint is set at the percentage of patients with detectable post-treatment circulating EBV-DNA has decreased from 30% to 10%.
Measured: From day of enrollment to the end of treatment at week 10
Secondary outcomes (1)
Determine the patient survival and recurrence rate post-treatment
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
Measured: 24 to 36 months after the last treatment done at week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study startApr 2026 (estimated)
- Primary completionApr 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Nasopharyngeal Carcinoma (NPC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07247201
- Sponsor's protocol ID
- 2024-2264
- Other IDs
- CSAINV22jul-0014, CTGIIT23jul-0003
- Acronym
- AlloNK1
- Status last verified
- Nov 2025
- First submitted
- 19 Nov 2025
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Goodman SN, Zahurak ML, Piantadosi S. Some practical improvements in the continual reassessment method for phase I studies. Stat Med. 1995 Jun 15;14(11):1149-61. doi: 10.1002/sim.4780141102.
PubMed 7667557Cheung, Y.K., Dose FInding by the Continual Reassessment Method. 2011: Chapman & Hall/CRC press.
cheung, Y.K., Coherence principles in dose-finding studies. Biometrika, 2005. 92: p. 10.
Yin, G. and Y. Yuan, Bayesian model averaging continual reassessment method in phase I clinical trials. Journal of the American Statistical Association, 2009. 104(487): p. 954-968.
O'Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics. 1990 Mar;46(1):33-48.
PubMed 2350571Jin YY, Yang WZ, Zou S, Sun ZY, Wu CT, Yang ZY. Chemoradiotherapy combined with NK cell transfer in a patient with recurrent and metastatic nasopharyngeal carcinoma inducing long-term tumor control: A case report. Medicine (Baltimore). 2020 Oct 23;99(43):e22785. doi: 10.1097/MD.0000000000022785.
PubMed 33120792Lin M, Luo H, Liang S, Chen J, Liu A, Niu L, Jiang Y. Pembrolizumab plus allogeneic NK cells in advanced non-small cell lung cancer patients. J Clin Invest. 2020 May 1;130(5):2560-2569. doi: 10.1172/JCI132712.
PubMed 32027620Ishikawa T, Okayama T, Sakamoto N, Ideno M, Oka K, Enoki T, Mineno J, Yoshida N, Katada K, Kamada K, Uchiyama K, Handa O, Takagi T, Konishi H, Kokura S, Uno K, Naito Y, Itoh Y. Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer. Int J Cancer. 2018 Jun 15;142(12):2599-2609. doi: 10.1002/ijc.31285. Epub 2018 Feb 14.
PubMed 29388200Hoogstad-van Evert J, Bekkers R, Ottevanger N, Schaap N, Hobo W, Jansen JH, Massuger L, Dolstra H. Intraperitoneal infusion of ex vivo-cultured allogeneic NK cells in recurrent ovarian carcinoma patients (a phase I study). Medicine (Baltimore). 2019 Feb;98(5):e14290. doi: 10.1097/MD.0000000000014290.
PubMed 30702598Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Shpall EJ, Lee DA, Champlin RE. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood. 2017 Oct 19;130(16):1857-1868. doi: 10.1182/blood-2017-05-785659. Epub 2017 Aug 23.
PubMed 28835441Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020 Mar;19(3):200-218. doi: 10.1038/s41573-019-0052-1. Epub 2020 Jan 6.
PubMed 31907401Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol. 2021 Feb;18(2):85-100. doi: 10.1038/s41571-020-0426-7. Epub 2020 Sep 15.
PubMed 32934330Han B, Mao FY, Zhao YL, Lv YP, Teng YS, Duan M, Chen W, Cheng P, Wang TT, Liang ZY, Zhang JY, Liu YG, Guo G, Zou QM, Zhuang Y, Peng LS. Altered NKp30, NKp46, NKG2D, and DNAM-1 Expression on Circulating NK Cells Is Associated with Tumor Progression in Human Gastric Cancer. J Immunol Res. 2018 Sep 3;2018:6248590. doi: 10.1155/2018/6248590. eCollection 2018.
PubMed 30255106Dianat-Moghadam H, Mahari A, Heidarifard M, Parnianfard N, Pourmousavi-Kh L, Rahbarghazi R, Amoozgar Z. NK cells-directed therapies target circulating tumor cells and metastasis. Cancer Lett. 2021 Jan 28;497:41-53. doi: 10.1016/j.canlet.2020.09.021. Epub 2020 Sep 26.
PubMed 32987138Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res. 2003;90:127-56. doi: 10.1016/s0065-230x(03)90004-2.
PubMed 14710949