Neoadjuvant CADI-05 in Combination With Pembrolizumab for Surgically Resectable Locally Advanced Head and Neck Squamous Cell Carcinomas (LA-HNSCC)
The goal of this clinical trial is to learn if drug CADI-05, when used together with pembrolizumab (an FDA approved immunotherapy), can help treat locally advanced head and neck squamous cell carcinoma (LA-HNSCC) in adults. It will also learn about the safety of drug CADI-05. The main questions it aims to answer are: * Does using CADI-05 together with pembrolizumab help the immune system fight cancer better and lead to better results for patients? * What side effects or health problems might happen when people receive these two treatments? Participants will: * Get pembrolizumab by IV (through a vein) once on day 1 of week 1 and again day 1 of week 4. This is standard of care treatment. * Get CADI-05 as a small injection into the skin once a week for 5 weeks. This is the experimental (research) treatment. * Visit the clinic every week for treatments, checkups and tests for 5 weeks. * Have surgery between week 6 and week 7. * Return to the clinic once for a follow-up visit about 30 days after surgery.
• Histologically confirmed new diagnosis of resectable, non-metastatic, squamous cell carcinoma that is either: Stage III Human Papillomavirus (HPV) positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M0); Stage III or IVA oropharyngeal HPV negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries (AJCC 8th edition) with programmed death ligand -1 (PD-L1) combined positive score (CPS) ≥ 1 (as determined by any clinical pathology laboratory) Patients must be planned for definitive surgical resection as determined by a multidisciplinary tumor board or equivalent multidisciplinary determination.
• Patients with recurrence or metachronous primary SCC of head and neck origins with previous history of surgery/radio (chemo)-therapy are allowed if definitive surgery is planned and if pembrolizumab is planned as a neoadjuvant strategy. Patients should have recovered from the effects of radiation or other prior treatments: AE/sequelae should resolve to ≤ grade 2 (no minimum recovery period required).
• Patients must have an archival biopsy from the primary tumor site or regional lymph nodal metastasis with adequate tumor tissue as judged by study PI. There should not be any oncological treatments between the pre-CADI-05 biopsy and W1 Pembrolizumab/CADI-05 treatment initiation. Note: If pretreatment material is a cytology specimen and deemed unsuitable for correlative testing, a core biopsy will be strongly recommended.
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Patients must consent to provide either archival (if available \& sufficient) or fresh pre-treatment tissue biopsy for research, and consent for the use of their residual post-operative tissue for research.
• Adequate bone marrow, liver and kidney function as demonstrated by:
‣ Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
⁃ Hgb \> 7 g/dL (use of transfusion to reach this threshold prior to study initiation is acceptable)
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.5
∙ upper limit of normal (ULN)
⁃ Total serum bilirubin ≤1.5 ULN
⁃ Patients with suspected Gilbert's disease may enroll provided that total bilirubin must be \< 3 mg/dL
⁃ Creatinine clearance (CrCL) \> 30 mL/min as measured via Cockcroft-Gault
• Female patients must be surgically sterile or be postmenopausal or must use highly effective contraception while receiving trial treatment.
• Subjects must possess the ability to understand and willingness to sign a written informed consent and HIPAA consent document. Translation services including translation of informed consent documents will be provided, as feasible, to encourage diversity of inclusion of eligible patients.