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CUE-101

Phase 2

Head and Neck Squamous Cell Carcinoma | Small molecule | Oncology |Cue Biopharma, Inc.|Last Updated: May 5, 2026

Target and mechanism

Molecular targetHPV16 E7
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment30

FDA Designations

No designations recorded

Clinical trial landscape

CUE-101 · 3 trials · 7 indications

Phase 2 2Phase 1 1
NCT07172256CUE-101with Pembrolizumab for LA-HPV+HNSCCsHead and Neck Squamous Cell Carcinoma
NOT YET_RECRUITING30 Analytics
NCT04852328Three 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 CarcinomaOropharyngeal Squamous Cell Carcinoma
RECRUITING30 Analytics
PHASE2NOT YET_RECRUITING
CUE-101with Pembrolizumab for LA-HPV+HNSCCs
Head and Neck Squamous Cell CarcinomaUnlock trial analytics
PHASE2RECRUITING
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
Oropharyngeal Squamous Cell CarcinomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Measurement of HPV-16 E711-20-Specific CD8+ T Cells in Peripheral Blood
Baseline and perioperative/periprocedural

This outcome measure evaluates the immune response by quantifying the presence of HPV-16 E711-20-specific CD8+ T cells in the peripheral blood at the conclusion of neoadjuvant treatment. The assessment will involve collecting blood samples from participants and analyzing them for the presence and quantity of these specific CD8+ T cells using immunological assays. The primary endpoint is the change in the number of HPV-16 E711-20-specific CD8+ T cells from baseline to the end of the treatment period.

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

-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
Through 12 month follow-up

* 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

Change in frequency of HPV16 E711-20 tetramer-positive cytotoxic T cell lymphocytes
Through 12 month follow-up

* 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

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
Dose Limiting Toxicity
36 months

The number of subjects who have dose limiting toxicities (DLTs), defined as clinically significant or ≥ Grade 3 Common Terminology Criteria for Adverse Events (CTCAE) v5.0, changes in adverse events (AEs), safety laboratory tests, physical examinations, electrocardiograms (ECGs), or vital signs

Serum PK parameters for CUE-101
36 months

Area under the concentration-time curve (AUC) of CUE-101

Secondary Endpoints

Assessment of Safety and Tolerability of CUE-101 Alone and in Combination with Pembrolizumab
Up to 30 days
Evaluation of Pathological Response Rate at End of Neoadjuvant Treatment
At screening and on the day of surgery
Evaluation of Radiologic Response Rate at End of Neoadjuvant Treatment
Baseline and perioperative/periprocedural
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Neoadjuvant CUE-101EXPERIMENTALNeoadjuvant therapy followed by definitive surgical resection
Neoadjuvant PembroEXPERIMENTALPembrolizumab Neoadjuvant therapy followed by definitive surgical resection
Neoadjuvant CUE-101 + PembroEXPERIMENTALCUE-101+Pembrolizumab as neoadjuvant therapy followed by definitive surgical resection
Schedule A: CUE-101EXPERIMENTAL* 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)
Schedule B: CUE-101EXPERIMENTAL* 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)
Schedule C: CUE-101EXPERIMENTAL* 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)
CUE-101 dose escalation and expansionEXPERIMENTALPart A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)
Pembrolizumab and CUE-101OTHERPart C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)

Interventions

NameTypeDescription
CUE-101DRUGCUE-101 will be administered by IV infusion with a commercially available syringe pump or IV infusion pump over 60 minutes on Day 1 and Day 21 after all procedures and assessments are completed. It will be administered at a dosage level of 4 mg/kg x 2
PembrolizumabDRUGPembrolizumab will be administered on Day 1 and Day 21 after all procedures and assessments are completed according to the Study Calendar. Pembrolizumab will be administered as a dose of 200 mg using a 30-minute (- 5 min/+10 min) IV infusion.
KEYTRUDA®, PembrolizumabDRUGKEYTRUDA® is first-line therapy in HPV16 and HLA A\*0201-positive recurrent and/or metastatic HNSCC patients given in combination with CUE-101 in Parts C\&D according to the schedule described in the protocol.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Participants must have histologically or cytologically confirmed new diagnosis of locally advanced, non-metastatic, head and neck squamous cell carcinoma of the oropharynx (cT1-4 N0-N3 M0) * Participants must be deemed unresectable by a head and neck surgeon for one or more of...

Countries:United States
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Frequently asked questions about CUE-101

What is CUE-101 used for?

CUE-101 is an investigational small molecule being developed for the treatment of head and neck cancer, specifically head and neck squamous cell carcinoma and oropharyngeal squamous cell carcinoma. It is being studied in patients with HPV16-positive tumors, including those with recurrent or metastatic disease and locally advanced disease.

What does CUE-101 target?

CUE-101 targets the HPV16 E7 protein, a viral oncoprotein expressed in HPV16-positive tumors. By targeting this antigen, the drug is designed to direct the immune system against cancer cells that present HPV16 E7, potentially offering a treatment approach for HPV-related head and neck cancers.

Who makes CUE-101?

CUE-101 is being developed by Cue Biopharma, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol CUE. The company is advancing the drug through clinical trials in the United States for the treatment of HPV16-positive head and neck cancers.

What phase is CUE-101 in?

CUE-101 is in Phase 1 and Phase 2 clinical trials. It has completed a Phase 1 study and is currently being evaluated in two Phase 2 trials. The drug is investigational and has not been approved by the FDA, as it remains in active clinical development.

What clinical trials is CUE-101 in?

CUE-101 is being studied in three clinical trials: NCT03978689, a completed Phase 1 study in HPV16+ recurrent or metastatic head and neck squamous cell carcinoma; NCT04852328, a recruiting Phase 2 trial in locally advanced HPV16-positive oropharyngeal squamous cell carcinoma; and NCT07172256, a Phase 2 trial not yet recruiting, combining CUE-101 with pembrolizumab in locally advanced HPV+ head and neck cancers.

Is CUE-101 the same as CUE-101 with pembrolizumab?

CUE-101 is the same drug in all its trials. In one ongoing Phase 2 study, NCT07172256, CUE-101 is being tested in combination with pembrolizumab for the treatment of locally advanced HPV-positive head and neck squamous cell carcinoma. This combination is being evaluated to assess the drug's effect when used alongside an immune checkpoint inhibitor.