‣ Informed consent

• Signed written and voluntary informed consent.

• Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

• Age \> 18 years, male or female.

• Disease characteristics

• Have histologically confirmed new diagnosis of non-metastatic squamous cell carcinoma as assessed by the Investigator based on baseline imaging and clinical assessment that is either:

∙ Stage III HPV-related oropharyngeal carcinoma OR

‣ Stage III, IVA and IVB HPV-unrelated oropharyngeal, laryngeal or hypopharyngeal carcinomas. Stage IVB oral cavity squamous cell carcinomas may be eligible upon consultation with Sponsor if considered unresectable as per treating surgeon and multidisciplinary tumor board.

⁃ According to UICC/AJCC 8th Edition staging

• Human papillomavirus (HPV)-relatedness in oropharyngeal primaries must be determined by positive p16 immunohistochemical staining on any tumor specimens and, if positive, confirmed by human papilloma virus (HPV) DNA testing by in situ hybridisation (ISH) or polymerase chain reaction (PCR). Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70 % or more of the tumor cells. Local testing is acceptable.

• Have an evaluable tumor burden assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) based on RECIST 1.1 as assessed by the local site investigator/radiology.

• Have provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for central biomarker analysis (fine needle aspirate (FNA) is not adequate).

• Repeat samples may be required if adequate tissue is not provided. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.

• Patient characteristics

• Eastern cooperative oncology group (ECOG) performance status 0-1.

• Patient must have adequate organ function as determined by the following:

• a. Hematology i. Absolute neutrophils \> 1.5 x 109/L ii. Platelets \> 100 x 109/L iii. Hemoglobin \> 90 g/L b. Biochemistry i. Bilirubin \< 1.5 x upper limit of normal (ULN) ii. aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 2.5 x ULN Note: Hematology test should be obtained without transfusion or receipt of colony stimulating factors within 4 weeks prior to obtaining sample.

• Specific criteria for Cohort A:

• iii. Creatinine clearance \> 60 mL/min as per cockcroft -gault formula iv. Not presenting with peripheral neuropathy \> grade 2 (CTCAE v5.0). v. Not presenting with clinically-significant hearing loss/tinnitus ≥ grade 3 (CTCAE v5.0).

• vi. 18-70 years old vii. Not presenting with cardiovascular disease: new york health association (NYHA) class II or higher, ischemic cardiovascular/cerebrovascular event in the past 12 months prior to inclusion in the study, clinically-significant peripheral arterial vasculopathy

• Specific criteria for Cohort B c. Patients considered unfit for cisplatin-based chemoradiotherapy, based on the following criteria (at least one): i. Creatinine clearance \>30 but \<60 mL/min ii. Impaired hearing loss/tinnitus ≥ grade 3 (CTCAE v5.0). iii. Peripheral neuropathy \> grade 2 (CTCAE v5.0). iv. Age \> 70 years old \* Patients \> 70 years old must be fit according to the G8 geriatric screening test (G8 \> 14 points)

⁃ Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

∙ Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).