Nivolumab & IRX-2 With Surgery for Resectable Stage III-IVA Oral Cavity Cancer or HPV-Positive Oropharyngeal Cancer

• Status: Withdrawn
• Trial end date: 2026-01-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects of nivolumab and IRX-2 and how well they work in treating participants with stage III-IVA oral cavity cancer or human papillomavirus (HPV)-positive oropharyngeal cancer that can be removed by surgery. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. IRX-2 may "turn on" the immune system and stimulate an immune response against tumor cells. Giving nivolumab and IRX-2 followed by surgery may work better at treating oral cavity and oropharyngeal cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborators: Bristol-Myers Squibb; Brooklyn ImmunoTherapeutics, LLC; IRX Therapeutics
• Treatments: Antibodies, Monoclonal; Cyclophosphamide; Nivolumab

Criteria

Inclusion Criteria:

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Pathologically confirmed (histology or cytology), p16-negative (by immunohistochemistry [IHC]) stage II, III, or IVA squamous cell cancer of the oral cavity (excluding lip)

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Disease is surgically resectable with curative intent

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Hemoglobin > 9 g/dL

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Lymphocyte count > 500/µL

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Neutrophil count > 1500/µL

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Platelet count > 100,000/µL

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Serum albumin > 3.0 g/dL

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT/ serum glutamate pyruvate transaminase [SGPT]) < 3 x the upper limits of normal (ULN)

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Alkaline phosphatase < 2 x ULN

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.4 x ULN

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Calculated creatinine clearance > 50 mL/min

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Willing and able to give informed consent and adhere to protocol therapy

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Eastern Cooperative Oncology Group (ECOG) performance status < 2

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Female of childbearing potential (less than 12 months post-menopausal) or male with a partner of childbearing potential either agrees to be abstinent or uses a medically acceptable form of birth control during the study and for a period of 1 year

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Negative urine/serum pregnancy test (female participants only) at the time of screening and within 24 hours of study treatment, if applicable

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Stage 1 (T1/2 N1) squamous cell carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments [CLIA] approved laboratory

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: No prior radiation above the clavicles

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Patients must not have evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Hemoglobin > 9 g/dL

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Lymphocyte count > 500/µL

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Neutrophil count > 1500/µL

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Platelet count > 100,000/µL

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Serum albumin > 3.0 g/dL

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Aspartate aminotransferase (AST/ SGOT) and alanine aminotransferase (ALT/ SGPT) < 3 x the upper limits of normal (ULN)

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Alkaline phosphatase < 2 x ULN

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.4 x ULN

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Calculated creatinine clearance > 50 mL/min

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Willing and able to give informed consent and adhere to protocol therapy

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: ECOG performance status < 2

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Female of childbearing potential (less than 12 months post-menopausal) or male with a partner of childbearing potential either agrees to be abstinent or uses a medically acceptable form of birth control during the study and for a period of 1 year

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Negative urine/serum pregnancy test (female participants only) at the time of screening and within 24 hours of study treatment, if applicable

Exclusion Criteria:

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior treatment with cetuximab or epidermal growth factor receptor (EGFR) inhibitors in any treatment setting

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any medical contraindications or previous therapy that would preclude treatment with either nivolumab, IRX-2, the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Clinical status of either subject or tumor such that administration of 10 day neoadjuvant IRX-2 before surgery would be medically inappropriate

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Primary tumor of the oropharynx

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:

• Involvement of pterygopalatine fossa, maxillary sinus, or facial skin

• Gross extension of tumor to the skull base

• Pterygoid plate erosion

• Sphenoid bone or foramen ovale involvement

• Direct extension to involve prevertebral fascia

• Extension to superior nasopharynx or Eustachian tube

• Direct extension into the neck with involvement of the deep neck musculature (neck node fixation)

• Suspected invasion (encasement) of the common or internal carotid arteries; encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270 degrees or greater

• Direct extension of neck disease to involve the external skin

• Direct extension to mediastinal structures

• Regional metastases to the supraclavicular neck (low level VB and IVB)

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any investigational agent within the previous 30 days

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Myocardial infarction within the last 3 months

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Evidence of distant metastases (M1 disease) or other concurrent primary malignancy

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Signs or symptoms of systemic infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Allergy to ciprofloxacin (or other quinolones) and acetylsalicylic acid

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations)

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior axillary dissection

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: History of pneumonitis or interstitial lung disease

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Any medical contraindications or previous therapy that would preclude treatment with either nivolumab or IRX-2 or the surgery, reconstruction or adjuvant therapy required to treat the oropharynx tumor appropriately

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Tumor of the oral cavity

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:

• Involvement of pterygopalatine fossa, maxillary sinus

• Gross extension of tumor to the skull base

• Pterygoid plate erosion

• Sphenoid bone or foramen ovale involvement

• Direct extension to involve prevertebral fascia

• Extension to superior nasopharynx or Eustachian tube

• Direct extension into the neck with involvement of the deep neck musculature (neck node fixation)

• Suspected invasion (encasement) of the common or internal carotid arteries; encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270 degrees or greater

• Direct extension of neck disease to involve the external skin

• Direct extension to mediastinal structures

• Regional metastases to the supraclavicular neck (low level VB and IVB)

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Any investigational agent within the previous 30 days

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Myocardial infarction within the last 3 months

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Evidence of distant metastases (M1 disease) or other concurrent primary malignancy

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Known infection with hepatitis B, hepatitis C, or HIV

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Signs or symptoms of systemic bacterial infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection)

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations)

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior axillary dissection

• HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: History of pneumonitis or interstitial lung disease