Inclusion Criteria:
1. Adult (≥18 years of age)
2. Disease-free cancer survivors evaluated at UT MD Anderson after treatment of squamous cell carcinoma (SCCA) of the oropharynx or HPV/p16+ SCCA of the head and neck of unknown primary
3. EMG evidence of XII neuropathy with no/equivocal physical examination signs, referred to in the protocol as "early/subclinical" CN XII neuropathy
4. Consent to parent cohort PA14-0947 for integrated longitudinal outcomes tracking in the OPC-SURVIVOR research program
5. The effects of Ajovy®- Fremanezumab on the developing human fetus are unknown. For this reason and because CGRP agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to treatment initiation and for the duration of study treatment and for 5 months after the last dose (covering \~5 half lives). (Refer to Pregnancy Assessment Policy UT MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure.
Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
6. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to treatment initiation and for the duration of study treatment and for 5 months after the last dose (covering \~5 half lives).
7. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. Primary surgery for OPC
2. Documented XII nerve injury by tumor or other non-cancer treatment source
3. History of multiple head and neck cancers or central nervous system cancer
4. Uncontrolled diabetes
5. Uncontrolled hypertension (systolic \>160; diastolic \>90)
6. Known gastrointestinal ulcer
7. History of psychiatric illness/social situations that would limit compliance with study requirements;
8. Untreated or treatment refectory obstructive pharyngoesophageal stricture
9. Known history or diagnosis of bipolar disorder
10. Functionally limiting cardiac, pulmonary, or neuromuscular disease
11. Recent acute coronary syndrome or stroke (within 3 months) or uncontrolled severe coronary artery disease with symptoms or coronary revascularization procedure (bypass surgery or stent within the last 3 months)
12. Hospitalization for heart failure or known NYHA Class III-IV heart failure within the previous 6 months.
13. Known ventricular arrhythmia requiring recent intervention (cardioversion, ablation, or antiarrhythmic initiation within 3 months), or currently symptomatic atrial fibrillation not rate-controlled.
14. Current or planned tracheostomy or total laryngectomy
15. Platelet \<50,000/mcL
16. Known hypersensitivity to fremanezumab-vfrm or any excipients (L-histidine, Lhistidine hydrochloride monohydrate, sucrose, disodium EDTA, polysorbate 80, water for injection)37
17. History of serious hypersensitivity reaction to another CGRP monoclonal antibody (erenumab, galcanezumab, eptinezumab)46
18. Pregnant and breastfeeding women are excluded from this study because the safety of Ajovy during pregnancy has not been established. Human data are insufficient to assess fetal risk, and as a monoclonal antibody, Ajovy may cross the placenta. It is also unknown whether Ajovy is present in human milk or what effects it may have on a breastfed infant. These potential risks may also apply to other agents used in this study. Pregnancy or women actively planning pregnancy during the treatment period37 and those Breastfeeding during the treatment period46
19. Currently taking the following medications: Other CGRP antagonists (biologic or small molecule): erenumab (Aimovig®), galcanezumab (Emgality®), eptinezumab (Vyepti®), rimegepant (Nurtec®), ubrogepant (Ubrelvy®), atogepant (Qulipta®)
20. Current cognitive or other limitations that preclude independent completion of study regimen
21. Patients who are receiving any other investigational agents.
22. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ajovy®- Fremanezumab or other agents used in study.
23. Current corticosteroid therapy prior to enrollment
24. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
