Inclusion Criteria:
1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of histologically confirmed locally recurrent (rT2-T4, N0-N1, M0) NPC (undifferentiated carcinoma with Epstein-Barr virus (EBV) infection by either presence of Epstein-Barr virus encoded RNA (EBER) in in-situ hybridization of the recently obtained tumor specimen before study entry) or an elevation of plasma EBV DNA in the subject's peripheral blood), staged according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging classification (TNM-8). All patients should NOT have received any form of anti-tumor treatment for their locally recurrent NPC before joining the study. However, prior radical treatment for their NPC at diagnosis is allowed if there is at least a 6-month interval between prior radical treatment and the start of study intervention of this study.
2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
3. Aged ≥18 years old
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
5. All eligible patients must be magnetic resonance imaging of T1, T2 and T1-contrast enhanced sequences of the head and neck region and PET-CT scan within 30 days of study entry.
6. Modified Charlson Comorbidity Score \<2
7. Adult Comorbidity Evaluation (ACE)-27 Index \<2
8. Pre-existing peripheral neuropathy \<=1
9. Have adequate organ function as defined in the following table (Table 5.1.1).
10. Body Weight \>30kg
11. For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to the start of treatment for their NPC. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women 1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
13. Must have a life expectancy of at least 12 weeks.
Exclusion Criteria:
1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
2. Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
3. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
4. Has had any prior monoclonal antibody before study entry, including but not limited to anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another costimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137 etc).
5. Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) before study entry. Patients who received radical radiation therapy and chemotherapy (but not immune checkpoint inhibitors or any form of immunotherapy) for their previously untreated nasopharyngeal carcinoma at diagnosis was allowed to join this study, provided that such radical treatment was completed \>6 months before study entry.
6. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation.
Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: Stage T1c or T2a with a Gleason score ≤6 and a prostate-specific antigen (≤10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.
7. Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis).
8. Has an active infection requiring intravenous systemic therapy or hospital admission.
9. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
12. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Routine checking for Anti-HIV1 or Anti-HIV2 is not mandatory.
13. Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA \[qualitative\] is detected) infection.
14. Has received a live vaccine 30 days prior to the first dose of trial treatment.
15. Has experienced Grade 4 toxicity on treatment with prior radiation.
16. Has experienced Grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation and/or chemotherapy.
17. Is taking \> 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required \> 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment.
18. Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody.
19. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade \>=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. (a) Patients with Grade \>=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. (b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with pembrolizumab may be included only after consultation with the Study Physician.
20. Major surgical procedure (as defined by the Investigator within 28 days prior to the first dose of IP. Local surgery of isolated lesions for palliative intent is acceptable.
21. History of allogenic organ transplantation.
22. History of leptomeningeal carcinomatosis.
23. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>=470ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
24. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>=470ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
25. Current or prior use of immunosuppressive medication within 14 days before the first dose of pembrolizumab. The following are exceptions to this criterion: (a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) (b) Systemic corticosteroids at physiologic doses not to exceed \<\> of prednisone or its equivalent (c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
