Ivonescimab for Kidney Cancer

Overseen By Pavlos Msaouel, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: PD-1/PD-L1 inhibitors

Must not be taking: Investigational agents

Disqualifiers: Other malignancies, Hypertension, Cardiac 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: 8

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug ivonescimab effectively controls advanced kidney cancer that has spread or returned after previous treatments. Participants must have clear cell renal cell carcinoma and have experienced disease progression after at least one prior treatment, including a specific type of immune therapy. The trial will test ivonescimab in two groups based on the treatments participants have already tried. This study might suit individuals whose kidney cancer has worsened after previous treatments and who have measurable disease activity. As a Phase 2 trial, this research focuses on assessing ivonescimab's effectiveness in an initial, smaller group, offering a potential new treatment option for participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it does allow for certain medications like anticoagulants and treatments for hepatitis B and C, provided they meet specific conditions. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that ivonescimab has been tested in patients with advanced solid tumors and generally has a manageable safety profile. While some side effects can occur, they are usually tolerable. Earlier studies found that ivonescimab has a short half-life, meaning the drug's level in the body decreases by half relatively quickly, which can sometimes result in shorter-lasting side effects.

Ivonescimab blocks two pathways, VEGF and PD-1, often involved in tumor growth and the body's immune response. This dual action can be effective but might also lead to side effects. However, evidence so far suggests these side effects are not severe.

In summary, ivonescimab appears well-tolerated based on studies with other advanced cancers, but like any treatment, it can have side effects. Clinical trial participants are closely monitored to manage any potential issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ivonescimab is unique because it targets both the immune system and blood vessels in kidney cancer. Unlike standard treatments, which might focus solely on inhibiting blood vessels, Ivonescimab combines an immune checkpoint blockade with anti-angiogenic properties. This dual action means it can potentially enhance the body's immune response against cancer cells while also cutting off the tumor's blood supply, making it a promising option for patients who have already tried other therapies. Researchers are excited because this approach could offer improved effectiveness and a new option for those with advanced kidney cancer.

What evidence suggests that ivonescimab might be an effective treatment for kidney cancer?

This trial will evaluate ivonescimab for treating advanced kidney cancer, specifically clear cell renal cell carcinoma (ccRCC), in patients who have tried other treatments. Studies have shown that ivonescimab may extend survival for some patients with this type of cancer. This investigational treatment targets cancer cells in a way that may enhance the immune system's ability to fight the disease. Although the full effectiveness is still under investigation, these early results are promising. ^{2 4 5 6 7}

Who Is on the Research Team?

Pavlos Msaouel, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced clear cell renal cell carcinoma (ccRCC) who've had at least one prior systemic treatment, including a PD-1/PD-L1 inhibitor. They must have measurable disease, stable cardiac function, and adequate organ/marrow function. Participants need to understand the study and consent to it, not be pregnant or breastfeeding, use contraception, and have no major diseases or recent surgeries.

Inclusion Criteria

Participants must have at least one measurable site of disease per RECIST version 1.1

INR and PT ≤ 1.5 x ULN and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 ULN

Participants must have the ability to understand and the willingness to sign a written informed consent document for this clinical trial and companion trials

Exclusion Criteria

Pregnant women, breastfeeding women, and women planning to breastfeed are excluded

History of major diseases prior to enrollment

Participants who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ivonescimab IV every 3 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The trial is testing Ivonescimab's effectiveness in controlling ccRCC that has been previously treated but continues to progress. It aims to see if this drug can help patients whose cancer has either locally advanced or spread further (metastatic).

How Is the Trial Designed?

Group I: Cohort 2 - (Post-ICB/VEGFTKI) Experimental Treatment 1 Intervention

Treatment with Ivonescimab IV Q3W

Group II: Cohort 1 - (Post-pure-ICB) Experimental Treatment 1 Intervention

Treatment with Ivonescimab IV Q3W

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Strategic Alliance

Collaborator

Trials

2

Recruited

90+

Summit Therapeutics Sub, Inc

Collaborator

Trials

1

Recruited

50+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Published Research Related to This Trial

Advanced renal cell carcinoma is resistant to many traditional therapies, but new immunotherapeutic approaches, including monoclonal antibodies and kinase inhibitors, are being explored, showing good tolerance and stable disease rates.

Two recently approved agents, a kinase inhibitor and an mTOR inhibitor, are now recommended as first-line treatments, while sorafenib is suggested for second-line therapy, highlighting the need for further research on their combinations and sequential use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current immunotherapeutic strategies in renal cell carcinoma. Amato, RJ.[2009]

Immunotherapy has been the leading treatment for advanced renal cell carcinoma, but its clinical effectiveness has been largely disappointing, prompting the search for better options.

New agents targeting specific biological abnormalities of renal cell carcinoma are currently being tested in clinical trials, showing promising early results that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Will the dark sky over advanced renal cell carcinoma soon become brighter? D'Hondt, V., Gil, T., Lalami, Y., et al.[2007]

Sunitinib has been established as the standard first-line treatment for advanced renal cell carcinoma, based on results from a large-scale, long-term Phase III trial.

Conventional treatments like nephrectomy followed by IL-2 or IFN-alpha often do not provide long-term survival benefits, highlighting the importance of targeted therapies like sunitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. Hutson, TE.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509606/

20: Phase II trial of ivonescimab in patients with advanced ... 20: Phase II trial of ivonescimab in patients with advanced clear cell renal cell carcinoma previously treated with immune checkpoint blockade: ...

2. cancernetwork.com cancernetwork.com/view/ivonescimab-displays-preclinical-feasibility-in-frontline-ccrcc

Ivonescimab Displays Preclinical Feasibility in Frontline ... The investigational agent exhibited superior efficacy vs pembrolizumab in patients with lung cancer, suggesting potential efficacy in kidney ...

3. urotoday.com urotoday.com/clinical-trials/kidney-renal-cancer/163689-phase-ii-trial-of-ivonescimab-in-previously-treated-patients-with-advanced-clear-cell-renal-cell-carcinoma.html

Phase II Trial of Ivonescimab in Previously Treated Patients ... Phase II Trial of Ivonescimab in Previously Treated Patients With Advanced Clear Cell Renal Cell Carcinoma.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06683846?tab=table

Ivonescimab in the Treatment of Multiple Advanced Tumors The goal of this clinical trial is to learn if Ivonescimab works to treat advanced rare tumors including cohort 1: PAGET's disease of scrotum with infiltrating ...

5. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2025/07/KCRS25-Abstract-Book-7.14.25.pdf

KCRS25 20 Phase II trial of ivonescimab in patients with advanced clear cell renal cell carcinoma previously treated ... improved overall survival in ...

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. cancernetwork.com cancernetwork.com/view/ivonescimab-shows-dual-inhibition-of-vegf-and-pd-1-pathways-in-ccrcc

Ivonescimab Shows Dual Inhibition of VEGF and PD-1 ... Treatment with the dual inhibitor displayed a short half-life and a manageable toxicity profile in patients with clear cell renal cell ...