A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

• Male or female and ≥ 18 years of age

• Histologically and/or cytologically confirmed primary diagnosis of R/M HNSCC

• Participants with oropharyngeal cancer will be required to have proof of p16negative status submitted on the basis of a pathology report

• At least 1 measurable lesion by contrast CT or MRI scan according to RECIST v.1.1.Such lesions must not have been previously irradiated; if the measurable lesion(s)has been irradiated, clear progression must be documented

• Participants must have failed prior therapy with an anti-PD-1/PD-L1 ICI and withplatinum-based chemotherapy administered in combination or sequentially, in eitherthe locally advanced or R/M setting. Failure of prior treatment may be due toprogression of disease or intolerance to treatment

• Patient's tumor must be considered inoperable and incurable

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a lifeexpectancy of at least 12 weeks

• For women of childbearing potential (WOCBP), documentation of negative serumpregnancy test within 30 days of randomization

• For WOCBP and male participants whose sexual partners are of childbearing potential,agreement to use an effective method of contraception during the study and for atleast 5 months after the last dose of study treatment. Birth control methods whichmay be considered highly effective include methods that achieve a failure rate ofless than 1% per year when used consistently and correctly.

• Ability to give written informed consent and comply with protocol requirements

• Patients with feeding tubes are eligible for the study.

• Archived tissue sample must be submitted to the Sponsor-designated laboratory within 60 days of randomization for c-Met analysis (if a tissue sample is not available, afresh biopsy may be required prior to enrollment)

Exclusion Criteria:

• Participants who have received > 2 prior lines of anticancer therapy or priortreatment with cetuximab/alternative EGFR inhibitors for the treatment of R/M HNSCC

• History of severe allergic or anaphylactic reactions or hypersensitivity torecombinant proteins or excipients in the investigational agent or cetuximab

• Known or suspected untreated and uncontrolled brain metastases or leptomeningealcarcinomatosis Note: Participants with locally treated brain metastases are eligibleprovided 2 weeks have elapsed since local therapy. Participants are allowed tocontinue steroid taper during the start of study treatment.

• Prior treatment with any other investigational drug or biologic agent or radiationtherapy before a washout has been completed (must be completed prior torandomization):

1. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeuticagents, small molecules, and checkpoint inhibitors

2. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drugconjugates

3. 4 weeks (28 days) for cell therapies

4. 2 weeks (14 days) for radiation therapy

• Any unresolved and significant toxicity (National Cancer Institute CommonTerminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) Grade > 2 fromprevious anticancer therapy (including radiation therapy), other than alopecia

• Significant cardiovascular disease, including: Cardiac failure New York HeartAssociation class III or IV; Myocardial infarction, severe or unstable angina within 6 months prior to randomization; History of serious ventricular arrhythmia (i.e.,ventricular tachycardia or ventricular fibrillation)

• Any other medical condition or psychiatric condition that, in the opinion of theInvestigator, might interfere with the participant's involvement in the study orinterfere with the interpretation of study results

• History of prior malignancy within 2 years prior to randomization (except foradequately treated non-melanoma skin cancer, carcinoma in situ of the breast orcervix, superficial bladder cancer, or early-stage prostate cancer, without evidenceof recurrence; participants may or may not be on maintenance therapy)

• Participants who are positive for HBV or HCV with indication of acute or chronichepatitis (as defined in protocol)

• Radiographic evidence (historical or at screening) of interstitial lung disease oridiopathic pulmonary fibrosis

• Female participants who are pregnant or breastfeeding

A full list of inclusion and exclusion criteria can be found in the protocol.