Neoadjuvant CADI-05 in Combination With Pembrolizumab for Surgically Resectable Locally Advanced Head and Neck Squamous Cell Carcinomas

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.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Biological: intradermal injection of CADI-05; Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianli Hu, MD, PhD; Phone Number: 267-449-1431; Email: Jianli.Hu@fccc.edu
• Study Contact Backup: Name: Parth Desai, MD, MBBS; Phone Number: 215-707-7777; Email: Parth.Desai@fccc.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Jianli Hu, MD, PhD; Phone Number: 267-449-1431; Email: Jianli.Hu@fccc.edu
      • Contact: Parth Desai, MD, MBBS; Phone Number: 215-728-4300; Email: Parth.Desai@fccc.edu
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Temple University Hospital
      • Contact: Jianli Hu, MD, PhD; Phone Number: 267-449-1431; Email: Jianli.Hu@fccc.edu
      • Contact: Parth Desai, MD, MBBS; Phone Number: 215-707-7777; Email: Parth.Desai@fccc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Patients who are considered candidates for organ preservation through upfront concurrent chemoradiation therapy will be excluded from this study.
• Receiving any investigational agent currently or within 28 days of first dose of CADI-05.
• Active, serious infection, medical, or psychiatric condition that would represent an inappropriate risk to the subject or would likely compromise achievement of the primary study objective, including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6 months prior to study entry.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease]; diverticulitis with the exception of a prior episode that has resolved or diverticulosis; celiac disease; irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; rheumatoid arthritis; hypophysitis, uveitis; etc.) within the past 2 years prior to the start of treatment. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

• Other prior or concomitant malignancies with the exception of:

  • Non-melanoma skin cancer
  • In-situ malignancy or any other malignancy that does not affect the primary management of the HNSCC under consideration including delivery of neoadjuvant pembrolizumab and definitive surgery plan.
  • Low-risk prostate cancer after curative therapy
  • Other cancer for which the subject has been disease free for ≥ 2 years before the first dose of study drug and of low potential risk for recurrence.
• Any concurrent chemotherapy, investigational treatment, biologic or hormonal therapy for cancer treatment except adjuvant intent hormonal therapy for definitively treated breast or prostate cancer that has not recurred in last 2 years. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable.
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of CADI-05. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (e.g. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiological doses not to exceed 10mg/day of prednisone or equivalent. [NOTE: If systemic corticosteroids are part of the treatment regimen for the indication under study, the systemic corticosteroid is permitted].
• Uncontrolled human immunodeficiency virus (HIV) infection with CD4+ T < 200 cells/mm3.
• Untreated or uncontrolled hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV). Patients with hepatitis B receiving treatment with anti- HBV therapy and having undetectable virus titers will be included.
• History of primary immunodeficiency.
• History of organ transplant.
• Pregnant or breastfeeding. Refer to section 4.4 for further detail.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment with CADI-05 and pembrolizumab; the neoadjuvant CADI-05 with pembrolizumab

Biological: intradermal injection of CADI-05; CADI-05 will be administered intradermally. Participants will receive 0.2 mL on Day 1 of Week 1, followed by 0.1 mL on Day 1 of Weeks 2, 3, 4, and 5. If needed for safety, the CADI-05 dose will be reduced, and only be administered at 0.1ml on Day 1 of Weeks 2, 3, and 5.; Biological: Pembrolizumab; Pembrolizumab (standard of care treatment) will be administered intravenously at a dose of 200 mg on Day 1 of Week 1 and Day 1 of Week 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of dose limiting toxicities (DLTs) by CTCAE ver. 6.0. of CADI-05 and pembrolizumab in patients with surgically resectable LA-HNSCC during the toxicity assessment window.	From Day 1 of CADI-05 treatment until safety follow-up, for a total of up to 13 weeks.
Occurrence of Grade 3 and higher AEs by CTCAE ver. 6.0. of CADI-05 and pembrolizumab in patients with surgically resectable LA-HNSCC during the toxicity assessment period at the MTD of CADI-05.	From the first treatment of CADI-05 through study completion, an average of 27 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The major pathological response (mPR) rates on post-treated surgical tumor specimens among patients treated at the MTD of CADI-05.	mPR is defined as the proportion of residual tumor cells was less than 10% of the total tumor involved in primary and draining nodal specimens from pathological examination of resected specimens.	At the time of surgery

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: Cadila Pharnmaceuticals
• Investigators: Principal Investigator: Parth Desai, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Surgery; Immunotherapy; Pembrolizumab; Neoadjuvant; Locally advanced; Squamous cell Carcinoma of Head and Neck; CADI-05
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; pembrolizumab
• Other Study ID Numbers: HN-227; 25-1040 (Other Identifier: Fox Chase Cancer Center IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No