A Study to Test Whether Treatment With BI 770371 in Combination With Pembrolizumab With or Without Cetuximab Helps People With Head and Neck Cancer Compared With Pembrolizumab Alone

Inclusion Criteria:

• Patients with histologically confirmed metastatic or recurrent HNSCC of the primarytumour location of oral cavity, oropharynx, hypopharynx, and larynx not amenable tolocoregional treatment with curative intent.

• Willingness to provide pretreatment (baseline) biopsy/tissue to the sponsor (freshor archival one). A newly obtained biopsy is preferred but an archival sample isacceptable, with tumor tissue (formalin fixed paraffin embedded [FFPE] blockpreferred, or at least 10 freshly sectioned unstained FFPE slides) from a core orexcisional biopsy. Any deviation from this rule requires approval by the sponsor.Details on the requirements for archival tumour tissue and on biopsy samplecollection are provided in the Laboratory Manual.

• Patients who have not received prior systemic treatment for metastatic or recurrentHNSCC. Systemic therapy (including cetuximab) which was completed more than 6 monthsprior to progression of disease if given as part of multimodal treatment for locallyadvanced disease is allowed.

• Patients who do not have contraindications to pembrolizumab monotherapy according topembrolizumab local label, guidelines, treatment standards, regulations or thedocument (label of another country if pembrolizumab local label is not available)provided in the investigator site file (ISF) by the sponsor.

• Patients who do not have contraindications to treatment with cetuximab according tocetuximab local label, guidelines, treatment standards, regulations, or the document (label of another country if cetuximab local label is not available) provided in theISF by the sponsor.

• Presence of at least one measurable non-central nervous system (CNS) lesion (according to RECIST v1.1.).

• Further inclusion criteria apply.

Exclusion Criteria:

• Nasopharyngeal carcinoma (NPC) of any histology, primary tumour location at nasalcavity, paranasal sinuses of any histology, any cancer of unknown primary.

• Any tumour location necessitating an urgent therapeutic intervention (e.g.,palliative care, surgery, or radiation therapy), such as spinal cord compression,other compressive mass, uncontrolled painful lesion, bone fracture.

• Patients with progressive HNSCC within 6 months of completion of systemic therapyfor locoregionally advanced disease with curative intent.

• Receiving treatment for brain metastases or leptomeningeal disease (LMD) which mayinterfere with safety and/or endpoint assessment. Patients with previously diagnosedbrain metastases are eligible if they have completed their treatment and haverecovered from the acute effects of radiation therapy or surgery prior to trialentry, have discontinued corticosteroid treatment for these metastases and areclinically stable, off anticonvulsants for at least 4 weeks and are neurologicallystable before enrollment.

• Patients for whom single agent pembrolizumab is not the preferred treatment (e.g.patients for whom chemotherapy or anti-PD-1 in combination with chemotherapy isconsidered the preferred therapy by the investigator or treating physician).

• Prior treatment with any anti signal regulatory protein alpha (SIRPα) oranti-integrin-associated protein (CD47) agent, regardless of treatment intent.

• Prior cancer treatment with any anti PD-1 or anti PD-L1 agent or with an agentdirected to another stimulatory or co-inhibitory Tcell receptor (e.g. CTLA-4, OX 40,CD137), regardless of treatment intent.

• Prior allogeneic stem cell or solid organ transplantation.

• Further exclusion criteria apply.