Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CUE-101 · 3 trials · 7 indications
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.
-Defined as \>7 days of treatment-related delay from the planned date of surgery or initiation of definitive-chemoradiation therapy.
* 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
* 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
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
Area under the concentration-time curve (AUC) of CUE-101
| Arm | Type | Description |
|---|---|---|
| Neoadjuvant CUE-101 | EXPERIMENTAL | Neoadjuvant therapy followed by definitive surgical resection |
| Neoadjuvant Pembro | EXPERIMENTAL | Pembrolizumab Neoadjuvant therapy followed by definitive surgical resection |
| Neoadjuvant CUE-101 + Pembro | EXPERIMENTAL | CUE-101+Pembrolizumab as neoadjuvant therapy followed by definitive surgical resection |
| 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) |
| 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) |
| 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) |
| CUE-101 dose escalation and expansion | EXPERIMENTAL | Part A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B) |
| Pembrolizumab and CUE-101 | OTHER | Part 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) |
| Name | Type | Description |
|---|---|---|
| CUE-101 | DRUG | CUE-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 |
| Pembrolizumab | DRUG | Pembrolizumab 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®, Pembrolizumab | DRUG | KEYTRUDA® 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. |
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...