Study of ALE.C04 in Patients With Head and Neck Cancer

Inclusion Criteria:

1. Be willing and able to provide written informed consents

2. Be 18 years of age on day of signing informed consent.

3. Have histologically or cytologically confirmed Recurrent or Metastatic (R/M) Headand Neck Squamous Cell Carcinoma (HNSCC) that is considered incurable by localtherapies.

4. Have provided tissue for claudin-1 (CLDN1), programmed death ligand-1 (PD-L1) andbiomarker analysis in a central Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.

5. Have measurable disease based on RECIST 1.1 as determined by the site.

6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)Performance Scale.

7. Have results from testing of human papillomavirus (HPV) status for oropharyngealcancer

Exclusion Criteria:

1. Has progressive disease (PD) within 6 months of completion of curatively intendedsystemic treatment for locoregionally advanced HNSCC (Phase II randomizedcombination part only).

2. Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior torandomization or patient has not fully recovered (i.e., ≤Grade 1 or at baseline)from adverse events due to a previously administered treatment. Palliativeradiotherapy to a limited field is allowed.

3. Severe immune-related adverse events leading to discontinuation of priorimmune-oncology agent only for Phase I dose escalation monotherapy and combinationand Phase II monotherapy.

4. Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis.

5. Dermatological conditions requiring active pharmacological treatment includingpsoriasis, atopic dermatitis, excessively dry skin or recurrent conjunctivitis,scleroderma, vitiligo, or any other active autoimmune dermatological disorder.

6. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the clinical study, interfere withthe patient's participation for the full duration of the clinical study, or is notin the best interest of the patient to participate, in the opinion of the treatinginvestigator.

7. Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1 oranti-PD-L2 (Phase II randomized combination part only).