Ivonescimab Before Surgery for the Treatment of Resectable Stage II-IV Head and Neck Cancer

NCT07094685 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UMCC 2025.012NCI-2025-04973HUM00273377
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well ivonescimab before surgery works in treating patients with stage II-IV head and neck cancer that can be removed by surgery (resectable). Ivonescimab is a bispecific monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A bispecific monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens).

Conditions

Advanced Head and Neck Squamous Cell Carcinoma; Resectable Head and Neck Squamous Cell Carcinoma; Stage II Head and Neck Cutaneous Squamous Cell Carcinoma; Stage III Head and Neck Cutaneous Squamous Cell Carcinoma; Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Major pathologic response rate

  The major pathologic response (MPR) rate is defined as the proportion of patients achieving major pathologic response out of all response-evaluable patients. This proportion will be estimated as the number of patients with MPR divided by the total number of patients response-evaluable for pathologic response. This estimate will be presented along with a Wilson score 95% confidence interval.

  Up to 36 months

Secondary Outcomes (3)

• Neoadjuvant ivonescimab related toxicities

  Up to 36 months

• Overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

  Up to 36 months

• Pathologic complete response rate

  Up to 36 months

Study Arms (1)

Treatment (ivonescimab)

EXPERIMENTAL

Patients receive ivonescimab IV over 60-120 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Then 4-8 weeks after last dose of ivonescimab, patient undergoes standard of care surgical dissection. Patients undergo PET-CT and may undergo biopsy at screening, as well as CT or MRI and collection of blood samples throughout the trial.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ivonescimab; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Surgical Procedure

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (ivonescimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ivonescimab)

Computed Tomography PROCEDURE

Undergo PET-CT and CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (ivonescimab)

Ivonescimab BIOLOGICAL

Given IV

Also known as: AK 112, AK-112, AK112, Anti-PD-1/Anti-VEGF Bispecific Antibody AK112, Anti-PD-1/VEGF Bispecific Antibody AK112, PD-1/VEGF Bispecific Antibody AK112, SMT 112, SMT-112, SMT112

Treatment (ivonescimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (ivonescimab)

Positron Emission Tomography PROCEDURE

Undergo PET-CT scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (ivonescimab)

Surgical Procedure PROCEDURE

Undergo surgical dissection

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (ivonescimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• PD-L1 combined positive score (CPS) \>= 1
• Histologically documented advanced stage mucosal HNSCC (stage II-IV), for which surgery would be recommended in routine clinical practice
• Primary tumor is amenable to fresh biopsy or availability of archival fresh frozen primary tissue
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Absolute neutrophil count \> 1500 cells/uL
• Platelet count \>= 100,000/uL
• Hemoglobin \>= 9.0 g/dL (without transfusion within 14 days prior to cycle 1, day 1)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) or =\< 3 x ULN for participants with Gilbert's disease
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN
• Creatinine =\< 1.5 x institutional ULN OR estimated glomerular filtration rate (eGFR) value \>= 30/mL using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation OR measured (OR calculated) creatinine clearance \>= 50 mL/min using the Cockcroft-Gault Formula
• Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g
• Prothrombin time (PT) or international normalized ratio (INR) =\< 1.5 x ULN, and partial thromboplastin time (PTT) or activated (a)PTT =\< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation
• For patients receiving therapeutic anti-coagulation there are no coagulation parameters for eligibility. However, patients should be on a stable dose
• Female patients of childbearing age per institutional definition must have negative serum pregnancy test results before enrollment

You may not qualify if:

• Prior radiation therapy for treatment of the current mucosal HNSCC (patients undergoing salvage resection are excluded)
• Prior neck dissection
• Major surgical procedures or serious trauma within 4 weeks prior to enrollment. Minor local procedures (excluding central venous catheterization, port implantation, and tumor biopsy) within 3 days prior to planned cycle 1, day 1
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment
• Nasal bleeding / epistaxis (bloody nasal discharge is allowed) graded as \>= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 within 14 days prior to registration
• Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as INR or aPTT is within therapeutic limits
• Patients with a condition requiring corticosteroid therapy (\> 10 mg prednisone/day or equivalent) within 14 days of the first dose of study drug. Exceptions: Physiologic replacement doses are allowed even if they are \> 10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder
• Patients with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date. Exceptions: Patients with vitiligo, type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that has resolved, or psoriasis that does not require systemic treatment are permitted
• Patients with symptomatic central nervous system (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis \>= 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease
• Recipient of a solid organ or allogeneic stem cell transplant
• Patients with active hepatitis B (Patients with stable or declining levels of hepatitis B deoxyribonucleic acid \[DNA\] by polymerase chain reaction \[PCR\] on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrollment will not be excluded)
• Patients with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV ribonucleic acid \[RNA\] levels above the lower limit of detection)
• Known allergy or hypersensitivity to any component of the study drug or any excipients (histidine, histidine hydrochloride, sucrose, polysorbate 80 (II), and water for injection); known history of severe hypersensitivity to other monoclonal antibodies
• Patient is breastfeeding or plans to breastfeed during study participation
• Radiographic evidence of major blood vessel encasement with narrowing of the vessel that the investigator determines will pose a significantly increased risk of bleeding

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Summit Therapeutics: collaborator

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Paul L Swiecicki

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Two head and neck pathologists will independently review the operative pathology to characterize a response. They will be blinded to each other's assessments.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 30, 2025
• Study Start: November 18, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): November 1, 2030
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)