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.
History of prior allogeneic bone marrow, stem-cell or solid organ transplantation
Distant metastases.
Treatment with radiation therapy or systemic anti-cancer therapy prior to the initiation of study drug administration.
Treatment with corticosteroids (>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration. Corticosteroids for topical, ophthalmic, inhaled, or nasal administration are allowed. Physiological replacement with hydrocortisone up to a maximum dose of 40 mg per day is allowed.
Sequential
CUE-101
DrugCUE Biopharma will supply CUE-101, which will be provided free of charge to the patient.
Number of treatment-related adverse events
Number of adverse events
Treatment-related delays in start of standard of care therapy
-Defined as \>7 days of treatment-related delay from the planned date of surgery or initiation of definitive-chemoradiation therapy.
Change in frequency of HPV16 E711-20-specific CD8+ T cells in peripheral blood samples
* Determined by IFN γ ELISpot for detection of HPV16 E711-20-specific T cells * Baseline, prior to each CUE-101 infusion, 24 hours post-end of each CUE-101 infusion, prior to standard of care therapy, at day 28 post CUE-101, 2 month follow-up, 4 month follow-up, 8 month follow-up and 12 month follow-up
Pathological tumor response
* Defined as rates of major and complete pathological response * A major pathologic response (mPR) will be defined as ≤ 10% residual viable tumor within the tumor sample collected after administration of CUE-101. A complete pathologic response (cPR) will be defined as no invasive cancer in the tumor sample collected. For surgical patients, the tumor sample will include the primary tumor specimen and all sampled regional lymph nodes at the time of resection. For def-chemoradiation therapy patients, the tumor sample will comprise the biopsy(s) submitted. Pathologic tumor response will be stratified based on if the patients underwent surgery or post-CUE-101 biopsy only.
Objective response rate (ORR)
* Proportion of patients with a complete response + partial response * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Change in area under the concentration-time curve (AUC) of serum PK parameters
-Prior to each CUE-101 infusion, end of each CUE-101 infusion, 1 hour post-end of each CUE-101 infusion, 5 hours post-end of each CUE-101 infusion, 24 hours post-end of each CUE-101 infusion, surgery day 1 or definitive chemoradiation day -2 or -1, 2 month follow-up, 4 month follow-up, 8 month follow-up and 12 month follow-up.
Change in Cmax of serum PK parameters
-Prior to each CUE-101 infusion, end of each CUE-101 infusion, 1 hour post-end of each CUE-101 infusion, 5 hours post-end of each CUE-101 infusion, 24 hours post-end of each CUE-101 infusion, surgery day 1 or definitive chemoradiation day -2 or -1, 2 month follow-up, 4 month follow-up, 8 month follow-up and 12 month follow-up.
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Washington University School of Medicine
Lead sponsor
Cue Biopharma
Collaborator
