Ivonescimab for Brain Tumors

Recruiting at 1 trial location

Overseen By Evguenia Gachimova, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Dexamethasone

Disqualifiers: Pregnancy, Hypertension, Cardiac disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ivonescimab (a PD-1/VEGF bi-specific antibody), to determine its effectiveness in treating recurrent glioblastoma, an aggressive brain tumor that returns after standard treatment. In the first phase, researchers aim to identify the safest and most effective dose. The second phase will assess whether this dose effectively controls the disease. This trial may suit individuals diagnosed with glioblastoma that has recurred after standard therapies like radiation or chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking dexamethasone at more than 2mg daily or need therapeutic anticoagulant therapy, you may not be eligible to participate.

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

Research has shown that ivonescimab is generally safe for humans. In one study, people with advanced lung cancer took ivonescimab with chemotherapy without major issues. Another study found that ivonescimab's side effects were mostly mild or manageable in patients with various advanced cancers. Additionally, when used for cancer that had spread to the brain, ivonescimab produced positive results, with some patients responding well. These findings suggest that ivonescimab is safe enough for continued testing in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ivonescimab is unique because it represents a new frontier in treating brain tumors by potentially activating the immune system against cancer cells. Unlike traditional treatments like chemotherapy and radiation, which directly target and kill cancer cells but can also damage healthy cells, Ivonescimab works by enhancing the body's natural immune response. Researchers are excited about Ivonescimab because it targets specific pathways that help the immune system recognize and attack tumor cells more effectively, offering hope for improved outcomes and fewer side effects compared to conventional therapies.

What evidence suggests that ivonescimab might be an effective treatment for brain tumors?

Research has shown that ivonescimab, a special type of antibody, offers promising results in treating brain-related conditions. In one study, ivonescimab helped shrink tumors in the brains of 34% of patients with cancer that had spread to the brain, effectively benefiting about a third of these patients. Additionally, ivonescimab has slowed the progression of certain lung cancers. While most current research focuses on lung cancer, its potential to treat brain tumors is encouraging. This trial will investigate ivonescimab's effectiveness in treating brain tumors like glioblastoma. ^{1 2 3 4 5}

Who Is on the Research Team?

Anuj D Patel, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent glioblastoma, a type of brain tumor. Participants should have experienced the return of their cancer after previous treatments. Specific eligibility criteria are not provided, but typically include factors like age, overall health status, and the absence of certain medical conditions.

Inclusion Criteria

I can care for myself but may need occasional assistance.

Recurrent supratentorial Glioblastoma that has progressed following standard therapy; patients must have previously been treated with radiation with or without temozolomide. Patients will be eligible at first or second recurrence. Patients must be greater than 12 weeks from completion of initial chemoradiation at the time of progression, with exceptions for patients with biopsy-confirmed recurrent disease prior to this time window. Diagnosis of Glioblastoma IDH-wildtype, WHO Grade 4 consistent with WHO CNS 2021 criteria. Measurable or evaluable disease per RANO criteria. A baseline MRI Brain no more than 14 days prior to study enrollment. Adequate Organ Function as per specified criteria. Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing. Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the ivonescimab. Male patients of childbearing potential having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until Day 120 after the last dose of ivonescimab. Ability to understand and willingness to sign informed consent form prior to the initiation of study and any study procedures.

Exclusion Criteria

Major surgical procedures or serious trauma within 4 weeks prior to randomization, or plans for major surgical procedures within 4 weeks after the first dose. Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to randomization. Currently pregnant or breastfeeding. History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to randomization. Current hypertension with specified blood pressure values. Is receiving dexamethasone >2mg daily, or the corticosteroid equivalent thereof. History of major diseases before randomization as specified. History of other malignancy diagnosed or requiring treatment within the past 3 years prior to enrolment, with exceptions. History of prior treatment with specified agents or therapies. Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multicentric disease. Uncontrolled seizures after best medical therapy or other neurological conditions. History of clinically significant autoimmune disease including but not limited to specified conditions. Has contraindication for undergoing MRI scans or receiving MRI contrast. History of stroke or TIA within 6 months prior to study enrolment. Imaging during the screening period shows that the patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or radiographic evidence of intratumor cavitation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive ivonescimab to determine the highest tolerable dose and recommended Phase 2 dose

12 weeks

Phase 2 Treatment

Participants receive the recommended Phase 2 dose of ivonescimab to assess disease control

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The study is testing ivonescimab to determine the highest dose patients can tolerate without severe side effects (Phase I) and to see if this dose can help control recurrent glioblastoma (Phase II).

How Is the Trial Designed?

Group I: Treatment with Ivonescimab Experimental Treatment 1 Intervention

Participants will be enrolled in either Phase 1 or Phase 2 depending on when they join the study.

Ivonescimab is already approved in China for the following indications:

Approved in China as Ivonescimab for:

• Locally advanced or metastatic non-squamous NSCLC

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Summit Therapeutics Sub, Inc

Collaborator

Trials

1

Recruited

50+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Published Research Related to This Trial

Evofosfamide combined with bevacizumab showed a 31% progression-free survival rate at 4 months in patients with bevacizumab-refractory glioblastoma, a significant improvement compared to the historical rate of 3%.

The treatment was generally safe, with 36% of patients experiencing grade 3-4 adverse events, but no grade 5 events, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Brenner, AJ., Floyd, J., Fichtel, L., et al.[2021]

In a Phase II study involving 31 Japanese patients with recurrent malignant glioma, single-agent bevacizumab demonstrated a 6-month progression-free survival rate of 33.9% and a median overall survival of 10.5 months, indicating its efficacy in this patient population.

Bevacizumab was well-tolerated, with manageable side effects; most notably, 79.3% of patients experienced disease control, and many were able to reduce or stop corticosteroid use during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma. Nagane, M., Nishikawa, R., Narita, Y., et al.[2022]

Evofosfamide (Evo) combined with bevacizumab (Bev) was well tolerated in a study of 28 patients with bevacizumab-refractory glioblastoma, with the maximum safe dose established at 670 mg/m2.

The treatment showed a 17.4% overall response rate and 60.9% disease control rate, indicating preliminary efficacy that warrants further research, especially in relation to tumor enhancement patterns and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study. Brenner, A., Zuniga, R., Sun, JD., et al.[2019]

The phase I study of the OX40 agonistic monoclonal antibody GSK3174998, alone or with pembrolizumab, was well tolerated among 138 patients with advanced solid tumors, with treatment-related adverse events occurring in 51% of patients in Part 1 and 64% in Part 2, but no maximum-tolerated dose was reached.

Despite demonstrating target engagement and some immune response changes in the tumor microenvironment, GSK3174998 showed limited clinical activity, with a disease control rate of only 9% in Part 1 and no significant improvement when combined with pembrolizumab, indicating it may not be viable for further development in advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). Postel-Vinay, S., Lam, VK., Ros, W., et al.[2023]

A new invasive glioblastoma model in mice showed that treatment with the anti-EGFR antibody cetuximab can significantly inhibit tumor growth, but only in tumors that have amplified or mutated EGFR, highlighting the importance of genetic factors in treatment efficacy.

In contrast, the anti-angiogenic antibody DC101 was ineffective against the diffusely invading glioblastomas, indicating that targeting angiogenesis may not be a viable strategy for these types of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2. Martens, T., Laabs, Y., Günther, HS., et al.[2020]

Monoclonal antibody 806 (mAb 806) effectively targets the mutant EGFR (de2-7 EGFR) found in gliomas, showing significant antitumor activity when combined with another antibody, mAb 528, in human xenograft mouse models.

The combination of mAbs 806 and 528 not only reduced the levels of de2-7 EGFR on tumor cells but also led to decreased tumor cell proliferation, suggesting a potential for enhanced therapeutic efficacy in treating gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity. Perera, RM., Narita, Y., Furnari, FB., et al.[2018]

In a study of 29 patients with symptomatic melanoma brain metastases receiving PD-1-directed therapy (ipilimumab plus nivolumab) alongside corticosteroids, the median overall survival was 5.45 months, with 21% of patients surviving after 3 years.

The overall response rate was 28%, and patients who responded to treatment had a significantly longer median overall survival of 56.4 months, indicating that while the benefits are modest, there is potential for long-term survival in responding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids. Manacorda, S., Carmena, MT., Malone, C., et al.[2023]

In a phase I study involving 40 patients with advanced cancers, the novel anti-VEGFR2 monoclonal antibody AK109 demonstrated a manageable safety profile, with no dose-limiting toxicities observed, although 38 patients experienced treatment-related adverse events, primarily proteinuria and hypertension.

AK109 showed promising preliminary antitumor efficacy, with a 10% objective response rate and a 62.5% disease control rate, leading to the selection of 12 mg/kg Q2W and 15 mg/kg Q3W as recommended phase II doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors. Zheng, Y., Zhong, H., Zhao, F., et al.[2023]

The recombinant human monoclonal antibody rhuMAb VEGF was safely administered to 25 patients with metastatic cancer, showing no severe adverse events directly related to the treatment, and only mild side effects like asthenia, headache, and nausea.

Pharmacokinetic analysis indicated a linear profile with a half-life of 21 days, suggesting that doses of 0.3 mg/kg or higher are comparable to other humanized antibodies, although no objective tumor responses were observed, with 12 patients maintaining stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. Gordon, MS., Margolin, K., Talpaz, M., et al.[2022]

Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, demonstrated promising efficacy in treating advanced non-small cell lung cancer (NSCLC), with an overall response rate (ORR) of 39.8% and a disease control rate of 86.1% among 108 patients studied over a median follow-up of 10.4 months.

The treatment was generally well tolerated, with only 22.2% of patients experiencing grade 3 or higher treatment-related adverse events, and a very low rate of treatment discontinuation (0.9%) due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. Wang, L., Luo, Y., Ren, S., et al.[2023]

In a case series of 13 patients with recurrent malignant glioma who had undergone a median of 5 prior therapies, the combination of bevacizumab and irinotecan resulted in a 77% rate of partial response and a median overall survival of 27 weeks, indicating significant efficacy in a heavily pretreated population.

The treatment was generally safe, although two patients experienced nonfatal intracranial bleeding, highlighting the need for monitoring while using this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases. Ali, SA., McHayleh, WM., Ahmad, A., et al.[2018]

Icrucumab, a monoclonal antibody targeting VEGFR-1, was safely administered to 26 patients with advanced solid tumors, showing no dose-limiting toxicities at doses up to 12 mg/kg, indicating a favorable safety profile.

The treatment resulted in stable disease in 23.1% of patients, with a median duration of 11.1 weeks, suggesting potential antitumor activity against various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. LoRusso, PM., Krishnamurthi, S., Youssoufian, H., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11033648/

Phase 1a dose escalation study of ivonescimab (AK112/ ... Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9087

Phase II results of ivonescimab (AK112/ SMT112), a novel ... Ivonescimab, plus chemotherapy has shown promising anti-tumor activity in pts with advanced/metastatic NSCLC without AGA and can be administered safely.

3. smmttx.com smmttx.com/pressrelease/promising-intracranial-anti-tumor-activity-and-safety-data-for-ivonescimab-in-nsclc-patients-with-brain-metastases-featured-at-elcc-2024/

Promising Intracranial Anti-Tumor Activity and Safety Data ... Ivonescimab alone or combined with chemotherapy led to intracranial responses among 34% of patients with brain metastases at baseline – 23% ...

4. prnewswire.com prnewswire.com/news-releases/ivonescimab-harmoni-a-study-final-os-analysis-results-presented-at-sitc-2025-with-os-hr0-74--302608764.html

Ivonescimab HARMONi-A Study Final OS Analysis Results ... This final OS analysis, the first from a Phase III trial of ivonescimab, confirms the breakthrough value of ivonescimab-based therapy in ...

5. akesobio.com akesobio.com/en/media/akeso-news/240908/

WCLC 2024 | Akeso's Ivonescimab Head-to-Head Phase III ... Ivonescimab as first-line treatment for PD-L1 positive NSCLC significantly extends median progression-free survival (mPFS) compared to pembrolizumab.