European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Male and female participants who are at least 18 years of age on the day of signinginformed consent with histologically confirmed diagnosis of squamous cell carcinoma (SCC) of the larynx or hypopharynx according to the decision of themultidisciplinary tumor board suitable for total laryngectomy can be enrolled inthis study.

2. Stage III, IVA or IVB, whenever clear resection margins R0 >5 mm can be achieved andno radiologic signs of extranodal extension of neck nodes are present.

3. Have provided newly obtained excisional biopsy of a tumor lesion not previouslyirradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred toslides.

4. PD-L1-expression* within the tumor biopsy, CPS ≥1

5. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 ofthis protocol during the treatment period and for at least 120 days after the lastdose of study treatment and refrain from donating sperm during this period.

6. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

7. Not a woman of childbearing potential (WOCBP) OR

8. A WOCBP who agrees to follow the contraceptive guidance during the treatmentperiod and for at least 120 days after the last dose of study treatment.

9. 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 date ofallocation/randomization.

10. Have adequate organ function as defined in the (Table 4) of the protocol. Specimensmust be collected within 10 days prior to the start of study treatment.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to receivingthe first dose of study medication (see Appendix 3). If the urine test is positiveor cannot be confirmed as negative, a serum pregnancy test will be required.

2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent orwith an agent directed to another stimulatory or co-inhibitory receptor on T or NKcells (e.g., CTLA-4, OX 40, CD137).

3. Has received prior systemic anti-cancer therapy including investigational agents.

4. Has received prior radiotherapy.

5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to thefirst dose of study drug. Administration of killed vaccines is allowed.

6. Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention.

7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of study drug.

8. Has a history of a second malignancy, unless potentially curative treatment has beencompleted with no evidence of malignancy for 2 years.

9. Has known distant metastases including active CNS metastases and/or carcinomatousmeningitis.

10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

11. Has active autoimmune disease that has required systemic treatment in the past 2years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment and is allowed.

12. Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease.

13. Has an active infection requiring systemic therapy.

14. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIVtesting is required unless mandated by local health authority.

15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] isdetected) infection. Note: no testing for Hepatitis B and Hepatitis C is requiredunless mandated by local health authority.

16. Has a known history of active TB (Bacillus Tuberculosis).

17. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with thesubject's participation for the full duration of the study, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

18. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

19. Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of trial treatment.

20. Has had an allogenic tissue/solid organ transplant.

21. Has a known intolerance to one of the substances administered during treatmentincluding e.g. antibiotics, antiemetics, etc. or any other component of concurrentauxiliary medication.