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

Trial Summary

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.

What data supports the effectiveness of the drug Ivonescimab for endometrial cancer?

While there is no direct data on Ivonescimab for endometrial cancer, similar treatments like pembrolizumab, an immune checkpoint inhibitor, have shown effectiveness in certain molecular subgroups of advanced recurrent endometrial cancer. These treatments work by helping the immune system recognize and attack cancer cells. ^{1 2 3 4 5}

What safety information is available for Ivonescimab in humans?

Ivonescimab, like other immune checkpoint inhibitors, can cause immune-related adverse events (irAEs), which are side effects that occur when the immune system attacks normal cells. Most irAEs are mild and manageable with medications like steroids, but some can be serious or life-threatening, affecting various organs and systems in the body. ^{6 7 8 9 10}

How is the drug Ivonescimab unique in treating endometrial cancer?

Ivonescimab is unique because it is being explored as a novel treatment option for endometrial cancer, which currently lacks a standard treatment, especially in advanced stages. While traditional treatments focus on chemotherapy and hormone therapy, Ivonescimab may offer a new approach by potentially targeting specific molecular pathways involved in the cancer's progression. ^{2 5 11 12 13}

What is the purpose of this trial?

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). The researchers will also look at whether the study drug is safe and causes few or mild side effects in participants.

Research Team

Maria Rubinstein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Ivonescimab in People With Endometrial and Cervical Cancers 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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Endometrial cancer: Molecular markers and management of advanced stage disease. [2020]

3. Switzerland 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial). [2022]

5. England pubmed.ncbi.nlm.nih.gov

Current opinion on bevacizumab on endometrial cancer treatment. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Optimizing Care for Patients With Adverse Events From Immunotherapeutics. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Strategies for improving the management of immune-related adverse events. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy. [2022]

9. United States 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Chemoresistance and targeting of growth factors/cytokines signalling pathways: towards the development of effective therapeutic strategy for endometrial cancer. [2020]