A Phase 2 Trial of Ivonescimab for Patients With Advanced, Metastatic Salivary Gland Cancers

NCT06805617 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-746
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to evaluate the efficacy and safety of Ivonescimab in participants with advanced, metastatic salivary gland cancers. The name of the study drug involved in this study is:

• Ivonescimab (a type of antibody)

Conditions

Salivary Gland Cancer; Advanced Salivary Gland Carcinoma; Metastatic Salivary Gland Cancer; Adenoid Cystic Carcinoma

Keywords

Salivary Gland Cancer; Salivary Gland Carcinoma; Metastatic Salivary Gland Cancer; Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) on treatment based on RECIST v1.1 criteria.

  Up to 2 years

Secondary Outcomes (6)

• Median Progression-Free Survival (PFS)

  Up to 2 years

• Median Overall Survival (OS)

  Up to 5 years

• Duration of Response (DOR)

  Up to 2 years

• Duration of Response [Cohort 1]

  Up to 2 years

• Duration of Response [Cohort 2]

  Up to 2 years

Study Arms (2)

Cohort 1: Adenoid Cystic Carcinoma

EXPERIMENTAL

Approximately 11 participants will be enrolled to this cohort in the first stage of recruitment. If there are ≤2 participants (out of 22) with responses to the therapy, the accrual to the study will be stopped. If there are \>2 participants with response, accrual will continue. Enrolled participants will complete: * Baseline visit * Imaging tests every 9 weeks * Cycle 1 through End of Treatment (21 day cycles) --Day 1: Predetermined dose of Ivonescimab 1x daily. * End of treatment visit with imaging * Follow up: every 12 weeks

Drug: Ivonescimab

Cohort 2: Non-Adenoid Cystic Carcinoma Salivary Gland Carcinoma

EXPERIMENTAL

Approximately 11 participants will be enrolled to this cohort in the first stage of recruitment. If there are ≤2 participants (out of 22) with responses to the therapy, the accrual to the study will be stopped. If there are \>2 participants with response, accrual will continue. Enrolled participants will complete: * Baseline visit * Imaging tests every 9 weeks * Cycle 1 through End of Treatment (21 day cycles) --Day 1: Predetermined dose of Ivonescimab 1x daily. * End of treatment visit with imaging * Follow up: every 12 weeks

Drug: Ivonescimab

Interventions

Ivonescimab DRUG

An immunoglobulin (Ig) G1 monoclonal antibody (mAb), single-use vial, via intravenous (into the vein) infusion per protocol.

Also known as: SMT112, AK112

Cohort 1: Adenoid Cystic Carcinoma; Cohort 2: Non-Adenoid Cystic Carcinoma Salivary Gland Carcinoma

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed salivary gland carcinoma (any histologic subtype, including ACC) with evidence of recurrent, metastatic, or advanced, unresectable disease.
• Willing to provide tumor tissue from a diagnostic biopsy or prior surgery if deemed safe and feasible by the investigator.
• Age 18 years or older at the time of consent. There is no upper age limit restriction in an effort to include patients across the lifespan.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participant must have organ and marrow function as defined below within 14 days prior to study registration:
• Absolute neutrophil count (ANC) ≥1000/mcL
• Hemoglobin ≥8.5 g/dL (with no blood transfusions within 7 days of start of therapy)
• Platelets ≥100,000/mcL
• Liver function:
• Serum total bilirubin (T-bili) ≤1.5× upper limit of normal (ULN); for patients with liver metastases or confirmed/suspected Gilbert syndrome, T-bili ≤3× ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× ULN; for patients with liver metastases, AST and ALT ≤5× ULN
• Creatinine Within normal limits, or Creatinine clearance (CrCl) ≥50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by BSA is not required for eGFR)
• Urine protein: Urine protein \<2+ or 24-hour urine protein quantification \<1.0 g
• Coagulation:prothrombin time (PT) or international normalized ratio (INR) ≤1.5× ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5× ULN (unless abnormalities are unrelated to coagulopathy or coagulation)
• Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study registration (progression of disease over any interval is allowed) and/or new or worsening disease-related symptoms within 12 months prior to study registration. This assessment is performed by the treating investigator. Evidence of progression by RECIST v1.1 criteria is not required.

You may not qualify if:

• Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment) and have no evidence of new or enlarging brain metastases.
• Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant or lactating women as the effects of the investigational therapy (ivonescimab) on the developing human fetus are unknown.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low- risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease in the last 2 years is permitted.
• Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Patients cannot be on long-term (\>4 weeks) corticosteroids at doses exceeding prednisone 10 mg daily (or its equivalent).
• Major surgical procedures or serious trauma within 4 weeks prior to starting therapy or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) are permitted.
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to the start of therapy, including but not limited to:
• a. Gastrointestinal bleeding
• b. Hemoptysis (defined as coughing up ≥0.5 teaspoon of fresh blood or small blood clots). Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
• c. Significant nasal bleeding/epistaxis (bloody nasal discharge is allowed)
• d. Need for therapeutic anticoagulant therapy within 14 days prior to the start of therapy.
• Current hypertension with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive therapy.
• History of major diseases , specifically:
• a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)

Sponsors & Collaborators

• Glenn J. Hanna: lead
• Summit Therapeutics: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Glenn J Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn J Hanna, MD

CONTACT

617-632-3090; glenn_hanna@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 3, 2025
• Study Start: February 26, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)