Ivonescimab for Salivary Gland Cancer

(I-MAC Trial)

Recruiting at 1 trial location

Overseen By Glenn J Hanna, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Glenn J. Hanna

Must not be taking: Corticosteroids, Anticoagulants

Disqualifiers: CNS metastases, Uncontrolled illness, Pregnancy, Autoimmune conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: Up to 2 years

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ivonescimab, an antibody, to determine its effectiveness and safety for individuals with advanced salivary gland cancer. The study focuses on patients whose cancer has spread or is inoperable. Participants will receive the treatment and undergo regular check-ups to monitor progress. This trial suits individuals with confirmed advanced or recurrent salivary gland cancer who have experienced disease progression or new symptoms in the past year. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take other cancer-specific therapies or investigational agents during the study.

Is there any evidence suggesting that Ivonescimab is likely to be safe for humans?

Research shows that Ivonescimab, the antibody under study, is still undergoing safety testing in humans. The study is in its second phase, indicating some early evidence of safety, but more information is needed for confirmation. In early studies, treatments at this stage are usually somewhat well-tolerated, meaning most patients can manage the side effects. However, specific details about side effects or negative reactions to Ivonescimab are not clearly available in the current information. Prospective participants should discuss known side effects and potential risks with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for salivary gland cancer?

Researchers are excited about Ivonescimab for salivary gland cancer because it offers a fresh approach to treatment. Unlike traditional therapies like surgery, radiation, and chemotherapy, which can be invasive or have significant side effects, Ivonescimab is an experimental drug that targets cancer cells directly. It works by inhibiting specific pathways that cancer cells use to grow, potentially leading to more effective and targeted treatment outcomes. This innovative mechanism of action holds promise for improving patient responses and reducing the burden of treatment.

What evidence suggests that Ivonescimab might be an effective treatment for salivary gland cancer?

This trial studies ivonescimab for its effectiveness in treating advanced salivary gland cancers. A previous study showed that ivonescimab effectively fights various cancers by targeting specific proteins that aid cancer cell growth and spread. For participants in Cohort 2, focusing on non-adenoid cystic carcinoma salivary gland carcinoma, early results suggest ivonescimab may shrink tumors or slow disease progression. In Cohort 1, which includes participants with adenoid cystic carcinoma, combining ivonescimab with chemotherapy significantly improved outcomes compared to other treatments. These findings highlight ivonescimab's potential as an effective option for treating advanced salivary gland cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Glenn J Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with advanced, metastatic salivary gland cancers, including adenoid cystic carcinoma. Participants should have a type of cancer that has spread and isn't responding to standard treatments.

Inclusion Criteria

I am fully active or can carry out light work.

At least one RECIST v1.1 measurable non-CNS based lesion

Ability to understand and sign a written informed consent document

Exclusion Criteria

I do not have any uncontrolled illnesses.

Concurrent administration of other cancer specific therapy or investigational agents

I have active brain metastases or cancer in my brain's lining.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Ivonescimab in 21-day cycles with imaging tests every 9 weeks

Up to 2 years

Cycle 1 through End of Treatment (21 day cycles), Imaging tests every 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Follow-up every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The study is testing the safety and effectiveness of Ivonescimab, an antibody designed to target cancer cells in patients with certain types of salivary gland cancers.

How Is the Trial Designed?

Group I: Cohort 2: Non-Adenoid Cystic Carcinoma Salivary Gland Carcinoma Experimental Treatment 1 Intervention

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

Group II: Cohort 1: Adenoid Cystic Carcinoma Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Glenn J. Hanna

Lead Sponsor

Trials

6

Recruited

160+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Published Research Related to This Trial

Ado-trastuzumab emtansine (T-DM1), a targeted therapy combining trastuzumab and a cytotoxic drug, showed excellent efficacy in treating a patient with HER2-positive parotid gland adenocarcinoma with brain metastasis.

This case suggests that targeting the HER2 pathway with T-DM1 could be a promising systemic chemotherapy option for patients with aggressive salivary gland carcinomas, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of ado-trastuzumab emtansine (T-DM1) in HER2 positive salivary gland tumour with brain metastasis. Dhamne, N., Koyyala, VPB., Chougule, S., et al.[2022]

Citations

1. smmttx.com smmttx.com/wp-content/uploads/2025/11/2025_PR_1107-SITC-HARMONi-A-Data-_-FINAL-v2.pdf

Ivonescimab Plus Chemotherapy Demonstrates a ... This review of overall survival at 52% data maturity and a data ... “Today's results highlight and support ivonescimab's differentiated efficacy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06805617

NCT06805617 | A Phase 2 Trial of Ivonescimab for ... 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 ...

3. akesobio.com akesobio.com/en/media/akeso-news/250907/

HARMONi Data Update Shows OS HR=0.78, Nominal P= ... This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared ...

4. cancertherapyadvisor.com cancertherapyadvisor.com/reports/ivonescimab-plus-chemo-efficacy-may-vary-across-populations/

Efficacy of Ivonescimab Plus Chemo May Vary Across ... The median OS was 16.8 months in the ivonescimab arm and 14.0 months in the control arm (HR, 0.79; 95% CI, 0.62-1.01; P =.0570). Among patients ...

5. prnewswire.com prnewswire.com/news-releases/ivonescimab-plus-chemotherapy-demonstrates-consistent-global-benefit-harmoni-data-update-shows-os-hr0-78--nominal-p0-0332--302548481.html

Ivonescimab Plus Chemotherapy Demonstrates Consistent ... This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06805617

NCT06805617 | A Phase 2 Trial of Ivonescimab for ... 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 ...

7. withpower.com withpower.com/trial/ivonescimab-for-salivary-gland-cancer-cd399

Ivonescimab for Salivary Gland Cancer (I-MAC Trial) This trial is for individuals with advanced, metastatic salivary gland cancers, including adenoid cystic carcinoma. Participants should have a type of cancer ...

8. go.drugbank.com go.drugbank.com/conditions/DBCOND0039494

Adenoid Cystic Carcinoma (DBCOND0039494) A Phase 2 Trial of Ivonescimab for Patients With Advanced, Metastatic Salivary Gland Cancers ... Adenoid Cystic Carcinoma and Other Salivary Gland Cancers.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8493384/

Systemic therapies for salivary gland adenoid cystic ... We surveyed the PubMed, summarized results of clinical trials, and discussed the potential clinical benefit of these therapies to ACC patients in the future.

10. accrf.org accrf.org/treatments/clinical-trials/open-studies/

Open Studies The table below lists clinical trials that currently are recruiting ACC patients in particular or salivary gland cancer patients. ... Ivonescimab (no prior VEGFR ...