A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients

Inclusion Criteria:

• Signed ICF before initiation of any study procedures.

• Age ≥ 18 years at signing of ICF.

• Histologically previously confirmed HNSCC with evidence of metastatic or locallyadvanced disease not amenable to standard therapy with curative intent.

• HNSCC patients progressed on or after anti-PD-1 therapy and platinum-containingtherapy.

• The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx,and larynx.

• Documentation of p16 status (positive or negative) by local laboratory IHC forpatients with primary oropharyngeal cancer.

• A baseline new tumor sample unless the patient has an available tumor sample as anFFPE block with sufficient material.

• Measurable disease as defined by RECIST v1.1 by radiologic methods.

• ECOG PS of 0 or 1

• Life expectancy ≥ 12 weeks, as per investigator

• Adequate organ function (as per protocol)

Exclusion Criteria:

• Central nervous system metastases that are untreated or symptomatic, or requireradiation, surgery, or continued steroid therapy to control symptoms within 14 daysof study entry.

• Known leptomeningeal involvement

• Any systemic anticancer therapy within 4 weeks of the first dose of study treatment.

• Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.

• Persistent Grade >1 clinically significant toxicities related to priorantineoplastic therapies

• History of hypersensitivity reaction to any of the excipients of treatment requiredfor this study.

• Unstable angina; history of congestive heart failure of Class II-IV New York HeartAssociation (NYHA) criteria, or serious cardiac arrhythmia requiring treatment orhistory of myocardial infarction within 6 months of study entry

• History of prior malignancies with the exception of excised cervical intraepithelialneoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at lowrisk for recurrence with no evidence of disease

• Current dyspnea at rest of any origin, or other diseases requiring continuous oxygentherapy

• Current serious illness or medical conditions including, but not limited to,uncontrolled active infection, clinically significant pulmonary, metabolic orpsychiatric disorders

• Patients with known infectious diseases (as per protocol)

• Pregnant or breastfeeding patients

• Patient has a primary tumor site of nasopharynx (any histology).