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

NCT04852328 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202106015
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (8)

• Number of treatment-related adverse events

  From start of treatment through 12 months after the completion of standard of care treatment (estimated to be 15 months)

• Number of adverse events

  From start of treatment through 12 months after the completion of standard of care treatment (estimated to be 15 months

• 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.

  From start of treatment through start of standard of care therapy (estimated to be 2 weeks)

• 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

  Through 12 month follow-up

• Change in frequency of HPV16 E711-20 tetramer-positive cytotoxic T cell lymphocytes

  * Determined by multiparameter flow cytometry * 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

  Through 12 month follow-up

• Change in frequency of HPV16 E711-20-specific CD8+ T cells in tumor samples

  Baseline, day -2 or -1 before start of standard of care therapy

• Activation markers of HPV16 E711-20 tetramer-positive cytotoxic T cell lymphocytes

  Through 12 month follow-up

• Proliferative status of HPV16 E711-20 tetramer-positive cytotoxic T cell lymphocytes

  Through 12 month follow-up

Secondary Outcomes (9)

• Pathological tumor response

  At the time of surgery or biopsy (Day 1 - approximately 7-14 days after start of CUE-101 treatment)

• Objective response rate (ORR)

  Prior to surgery/definitive chemoradiation treatment (Day 1 - approximately 7-14 after start of CUE-101 treatment)

• Change in area under the concentration-time curve (AUC) of serum PK parameters

  Through 12 month follow-up

• Change in Cmax of serum PK parameters

  Through 12 month follow-up

• Change in Terminal elimination half-life(t1/2) of serum PK parameters

  Through 12 month follow-up

Study Arms (3)

Schedule A: CUE-101

EXPERIMENTAL

* In Schedule A, CUE-101 will be administered during the neoadjuvant phase as a single dose given 14 days prior to initiation of standard of care (SOC) therapy. * Standard of care therapy consists of surgery and postoperative adjuvant (cisplatin) and radiation therapy or cisplatin and radiation therapy (definitive-chemoradiation therapy)

Drug: CUE-101

Schedule B: CUE-101

EXPERIMENTAL

* In Schedule B, CUE-101 will be administered during the neoadjuvant phase as two doses: one dose given 14 days and one dose given 7 days prior to initiation of standard of care (SOC) therapy. * Standard of care therapy consists of surgery and postoperative adjuvant (cisplatin) and radiation therapy or cisplatin and radiation therapy (definitive-chemoradiation therapy)

Drug: CUE-101

Schedule C: CUE-101

EXPERIMENTAL

* In Schedule C, CUE-101 will be administered during the neoadjuvant phase as a single dose given 7 days prior to initiation of standard of care (SOC) therapy. * Standard of care therapy consists of surgery and postoperative adjuvant (cisplatin) and radiation therapy or cisplatin and radiation therapy (definitive-chemoradiation therapy)

Drug: CUE-101

Interventions

CUE-101 DRUG

CUE Biopharma will supply CUE-101, which will be provided free of charge to the patient.

Schedule A: CUE-101; Schedule B: CUE-101; Schedule C: CUE-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• History of clinically significant cardiovascular disease including:
• Myocardial infarction or unstable angina within the 16 weeks prior to the initiation of study drug
• Clinically significant cardiac arrhythmias
• Uncontrolled hypertension: systolic blood pressure \>180 mmHg, diastolic blood pressure \>100 mmHg
• Deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack within the 16 weeks prior to the initiation of study drug
• QTc prolongation \> 480 msec
• Congestive heart failure (New York Heart Association class III- IV)
• Pericarditis/clinically significant pericardial effusion
• Myocarditis
• Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen).
• Clinically significant gastrointestinal (GI) disorders including history of:

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Cue Biopharma: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Douglas Adkins, M.D.

CONTACT

314-747-8475; dadkins@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2021
• First Posted: April 21, 2021
• Study Start: December 6, 2021
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)