This Phase 2a/2 study evaluates the safety, tolerability, and efficacy of neoadjuvant and adjuvant NAI, hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel in participants with locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The study includes a Phase 2a safety lead-in followed by a randomized Phase 2 comparison of a de-intensified experimental chemoradiation approach versus standard-of-care chemoradiation.
Age ≥ 18 years old.
Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically confirmed squamous cell carcinoma of the oropharynx that is HPV-positive (p16 immunohistochemistry positive and/or HPV DNA positive). Patients with cervical lymph node metastases from an unknown primary can be included if p16-positive and likely OPSCC origin.
Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Per cisplatin prescribing information, female participants of child-bearing potential must agree to use effective contraception for up to 14 months and non-sterile male participants must agree to use a condom for up to 11 months after last dose of cisplatin. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.
HPV-negative or Non-OPSCC: Tumors that are p16-negative or not in the oropharynx are excluded.
Any evidence of distant metastases (M1 disease) excludes the patient, since the trial is for curative-intent local/regional therapy.