Ivonescimab for Endometrial Cancer

Recruiting at 6 trial locations

Overseen By Vicky Makker, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Active hepatitis, Autoimmune disease, Heart disease, 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: 1

Duration: 24 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of ivonescimab for people with endometrial or cervical cancer. Participants will receive ivonescimab to determine its ability to control cancer with minimal side effects. Suitable candidates have endometrial or cervical cancer that has returned after at least one round of platinum-based treatment and are managing metastatic or recurrent conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on therapeutic anticoagulant therapy, you may need to stop it 14 days before enrolling. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that ivonescimab has a manageable safety profile. While side effects can occur, they are generally mild and manageable. Common side effects include anemia (low red blood cell count), proteinuria (protein in urine), and decreases in certain immune cells. These effects are typical and manageable for treatments like this.

Research shows that ivonescimab boosts the immune system to fight cancer cells. This can sometimes cause immune-related side effects, but they are usually mild and less severe than those from traditional chemotherapy.

Overall, studies so far suggest that ivonescimab is well-tolerated. Prospective trial participants should discuss any specific concerns with their healthcare provider, who can provide more details based on individual health needs. ^{1 2 3 4 5}

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

Ivonescimab is unique because it targets endometrial cancer in a new way. Most treatments for this condition, like chemotherapy and hormone therapy, work by slowing or stopping cancer cell growth indirectly. Ivonescimab, however, is an innovative antibody that directly targets cancer cells, potentially enhancing the immune system's ability to attack the tumor. Researchers are excited about this treatment because it offers a promising alternative that could improve outcomes for patients with fewer side effects.

What evidence suggests that ivonescimab might be an effective treatment for endometrial and cervical cancer?

This trial will evaluate ivonescimab as a treatment for both endometrial and cervical cancer. Studies have shown that ivonescimab may be a promising treatment for these cancers. In earlier research, about 25% of patients experienced a significant reduction in tumor size with ivonescimab, meaning roughly one in four patients saw their tumors shrink noticeably. Ivonescimab boosts the immune system's ability to fight cancer cells, which can lead to smaller tumors. For cervical cancer, ivonescimab has also improved survival rates compared to some other treatments. These findings suggest that ivonescimab could be an effective option for treating these types of cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Maria Rubinstein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with endometrial cancer (EC) or cervical cancer (CC). Specific eligibility criteria are not provided, but typically participants must have a confirmed diagnosis and meet certain health standards set by the researchers.

Inclusion Criteria

Measurable disease per RECIST v 1.1 criteria

Have adequate laboratory values as defined in the protocol

Not Pregnant and Not Nursing. If with childbearing potential, should have a negative urine pregnancy test at the time of screening

Exclusion Criteria

Prolongation of QTc interval to >480 msec

I have been part of a cancer study and received treatment less than 4 weeks ago.

I currently have an active Hepatitis B infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivonescimab treatment every 3 weeks for up to 24 months

24 months

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

27 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The study is testing ivonescimab to see if it's an effective treatment for EC and CC. It will also assess the safety of ivonescimab and monitor the severity of any side effects in those taking part in the trial.

How Is the Trial Designed?

Group I: Ivonescimab in People With Endometrial Cancer Experimental Treatment 1 Intervention

Study treatment will be given sequentially on the first day of each cycle in a 3-week dosing cycle: Ivonescimab will be administered as 20 mg/kg IV (a fixed dose of 3200 mg for ivonescimab should be used for patients ≥ 160 kg), Q3W administered for 60 minutes (± 10 minutes). The total duration of ivonescimab treatment is up to 24 months.

Group II: Ivonescimab in People With Cervical Cancer Experimental Treatment 1 Intervention

Study treatment will be given sequentially on the first day of each cycle in a 3-week dosing cycle: Ivonescimab will be administered as 20 mg/kg IV (a fixed dose of 3200 mg for ivonescimab should be used for patients ≥ 160 kg), Q3W administered for 60 minutes (± 10 minutes). The total duration of ivonescimab treatment is up to 24 months.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Summit Therapeutics Sub, Inc

Collaborator

Trials

1

Recruited

50+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Published Research Related to This Trial

Endometrial cancer, the most common gynecologic cancer in the U.S., is seeing rising death rates, but recent advancements in precision medicine, including the FDA approval of pembrolizumab for tumors with defective DNA mismatch repair, offer new hope for 20-30% of advanced cases.

Current research is focused on identifying effective biomarkers for targeted therapies, as single-agent treatments have shown only modest efficacy, and future clinical trials will explore novel combinations and the use of advanced genomic data to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial cancer: Molecular markers and management of advanced stage disease. Arend, RC., Jones, BA., Martinez, A., et al.[2020]

Immune checkpoint inhibitors (ICPis) can lead to significant and durable responses in hard-to-treat cancers, but they also cause immune-related adverse events (irAEs) due to excessive T-cell activity, which can be life-threatening in some cases.

There is an urgent need for improved management strategies for irAEs, including patient education, standardized reporting and treatment guidelines, and the use of technology to personalize care, as the incidence of these side effects is expected to rise with the increased use of ICPis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for improving the management of immune-related adverse events. Naing, A., Hajjar, J., Gulley, JL., et al.[2021]

Immune checkpoint blockade (ICB) therapies, which enhance the immune system's ability to fight cancer, can lead to serious dermatologic adverse events (DAEs) such as Stevens-Johnson syndrome and toxic epidermal necrolysis, potentially limiting their use.

Proper identification and management of these high-grade DAEs are crucial, as they may indicate a positive response to cancer treatment and patients often have few alternative options for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer. Kuo, AM., Markova, A.[2022]

Pembrolizumab and dostarlimab, immune checkpoint inhibitors, have been approved for treating advanced recurrent endometrial cancer in patients with specific molecular subgroups, particularly those with mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) status, based on data from 15 studies involving 1609 patients.

The combination of pembrolizumab or dostarlimab with lenvatinib has shown efficacy in patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) endometrial cancer, highlighting the importance of biomarker assessment to optimize treatment strategies for different molecular phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis. Johnson, RL., Ganesan, S., Thangavelu, A., et al.[2023]

A meta-analysis of 21 studies involving 11,144 patients revealed that anti-CTLA4 therapy significantly increases the risk of various immune-related adverse events, such as diarrhea and colitis, with a relative risk of 2.43 to 11.39 for different conditions.

In contrast, while anti-PD1 therapy also raises the risk of pruritus (itching) with a relative risk of 4.01, it does not appear to increase the risk of other immune-related adverse events, highlighting the distinct safety profiles of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies. Komaki, Y., Komaki, F., Yamada, A., et al.[2022]

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., et al.[2022]

Immune-related adverse events (irAEs) are common but mostly mild and manageable with steroids in patients receiving immune checkpoint inhibitors, highlighting the importance of effective management strategies as these therapies become more widely used.

The study outlines a comprehensive 3-pronged strategy for managing irAEs, including a dedicated Immune Wellness Clinic for monitoring at-risk patients, a repository for supporting research, and an Immunotoxicity Tumor Board for handling severe cases, which can enhance patient care and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Care for Patients With Adverse Events From Immunotherapeutics. Sheehan, K., Price, C., Hafez, N.[2021]

Immunotherapy has revolutionized cancer treatment, becoming a standard approach for various cancer types, but it also introduces a wide range of adverse events affecting multiple organ systems.

The review highlights the increasing occurrence of uncommon immune-related adverse events (affecting less than 1% of patients) as immunotherapy use expands, emphasizing the need for better awareness and diagnostic strategies among healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy. Albarrán-Artahona, V., Laguna, JC., Gorría, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06925724

NCT06925724 | A Study of Ivonescimab in People With ... The researchers are doing this study to find out if ivonescimab is an effective treatment for people with endometrial cancer (EC) and/or cervical cancer (CC).

2. 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 ...

3. 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 ... With a median follow-up of 32.5 months, the long-term safety profile of the ivonescimab combination therapy remained favorable, with no new ...

4. smmttx.com smmttx.com/pressrelease/https-www-smmttx-com-wp-content-uploads-2025-09-2025_pr_0907_wclc-harmoni-data-_-final-pdf/

Longer-Term Follow-Up of Western Patients Showed ... With Longer-Term Follow-Up of Western Patients, Ivonescimab Plus Chemotherapy Demonstrated Improving Global OS Trend with Nominal p-value of ...

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

Efficacy of Ivonescimab Plus Chemo May Vary Across ... Overall survival (OS) data were presented for all 438 patients. At a median follow-up of 29.7 months, there was a trend toward improved OS with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11925807/

Safety, Pharmacokinetics, and Pharmacodynamics Evaluation ... We report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ivonescimab in patients suffered from advanced solid tumors.

7. smmttx.com smmttx.com/wp-content/uploads/2024/09/2024_PR_0916_ESMO-2024-Data-_-FINAL.pdf

Promising Anti-Tumor Activity and Safety of Ivonescimab in ... The most common TRAEs were anemia, proteinuria, white blood cell count decreases, and neutrophil count decreases in this Phase II data set.

8. jitc.bmj.com jitc.bmj.com/content/12/4/e008037

Phase 1a dose escalation study of ivonescimab (AK112 ... In summary, ivonescimab demonstrated manageable safety and tolerability profile. Preliminary efficacy data showed encouraging efficacy signals ...

9. akesobio.com akesobio.com/en/media/akeso-news/240906/

Akeso to Present Data from 13 Clinical Studies at ESMO ... Ivonescimab demonstrated robust ORR and DCR. PFS results were meaningfully significant, even in patients with limited follow-up time and ...