Non-Randomized Phase 2 Trial of Three Schedules of CUE-101 Administered Before Surgery or Definitive Chemoradiation Therapy in HLA-A*0201 Positive Patients With Locally Advanced, HPV16-Positive Oropharyngeal Squamous-Cell Carcinoma
This is a phase 2 trial to assess the safety and tolerability of three schedules of CUE-101 administered in the neoadjuvant phase before standard of care (SOC) therapy to treatment naïve, HLA-A\*0201 positive patients with newly diagnosed, locally advanced HPV16+ oropharyngeal squamous-cell carcinoma (OPSCC). This is an exploratory trial of a limited sample size to confirm safety and to assess for pharmacodynamic signals of efficacy in each of three schedules of CUE-101. Safety assessments will be performed at baseline and after CUE-101 administration. To assess for efficacy, peripheral blood and tumor samples will be collected at baseline and after CUE-101 administration. Following CUE-101, patients will proceed with SOC therapy, as prescribed by the treating physician.
• Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma of the oropharynx or of an upper (levels 2-3) neck mass without a known primary site, but is suspected to be oropharynx based on clinical factors.
• Stage I-III (AJCC 8th Edition) \[except clinical stages T1N0 and T2N0, which are excluded from enrollment\].
• A candidate for standard of care therapy (either surgery followed by adjuvant therapy OR def-CRT), based on treating physician decision.
• HLA-A\*0201 genotype as determined by genomic testing on blood sample performed at a CLIA-certified clinical or central laboratory.
• Tumors must test positive for HPV16 by PCR (performed on tumor) or ISH (performed in tumor) and p16INK4A expression (\>70% staining in tumor cells) by IHC performed at a CLIA-certified clinical or central laboratory.
• Have archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion of sufficient size and quality for eligibility determination.
• At least 18 years of age.
• ECOG performance status ≤ 1.
• Normal bone marrow and organ function as defined below:
‣ Platelets ≥ 100,000/mcl
⁃ Hemoglobin ≥ 9.0 g/dL
⁃ Absolute neutrophil count ≥ 1,500/mcl
⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
⁃ Total bilirubin ≤ 1.5 x IULN, except patients with Gilbert's syndrome, who may enroll if the conjugated bilirubin (total and direct) is within normal limits
⁃ Creatinine \< 1.5 mg/dL, or calculated or measured creatinine clearance \>30 mL/min by Cockcroft-Gault
⁃ Note: Screening laboratory tests may be repeated once within 7 days.
• The effects of CUE-101 on the developing human fetus are unknown. For this reason and because novel Fc Fusion Protein agents 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 study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 30 days after completion of the study.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.