MEDI5752 + Axitinib/Lenvatinib for Kidney Cancer

Recruiting at 15 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MedImmune LLC

Must not be taking: mTOR inhibitors, Immune checkpoint inhibitors

Disqualifiers: Infections, Autoimmune disorders, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

67 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop all current medications. However, you cannot use immunosuppressive medication within 14 days before starting the trial, and you must not change antihypertensive medications within 1 week before starting. Also, any concurrent cancer therapy is not allowed.

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

The trial requires that you stop using immunosuppressive medications at least 14 days before starting the study treatment. If you have poorly controlled blood pressure, you must stabilize it and avoid changing antihypertensive medications within one week before starting the trial.

What data supports the idea that MEDI5752 + Axitinib/Lenvatinib for Kidney Cancer is an effective drug?

The available research shows that combinations similar to MEDI5752 + Axitinib/Lenvatinib, like axitinib plus pembrolizumab, have been effective in treating advanced kidney cancer. For example, axitinib plus pembrolizumab has a 73% response rate in patients with advanced renal cell carcinoma. Additionally, lenvatinib plus pembrolizumab has shown improved survival rates compared to other treatments like sunitinib. These combinations are recommended as first-line treatments for advanced kidney cancer, indicating their effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination MEDI5752 + Axitinib/Lenvatinib for kidney cancer?

Research shows that combining axitinib with pembrolizumab, a similar type of drug to MEDI5752, has a high response rate and improves survival in advanced kidney cancer. Additionally, lenvatinib combined with pembrolizumab has shown benefits in survival and response rates, suggesting potential effectiveness when used with similar drugs. ^{1 2 3 4 5}

What safety data exists for the treatment of MEDI5752 with Axitinib or Lenvatinib for kidney cancer?

The safety data for treatments involving Axitinib and Lenvatinib in combination with immune checkpoint inhibitors (ICIs) like pembrolizumab have been explored in several studies. The CLEAR study showed that Lenvatinib plus pembrolizumab improved survival outcomes in advanced renal cell carcinoma, with common adverse reactions being characterized and management strategies reviewed. Axitinib combined with pembrolizumab has been studied for its safety and antitumor activity, with recommendations for managing adverse events such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues. These combinations are part of the standard care for advanced kidney cancer, with safety and efficacy data supporting their use. ^{1 4 6 7 8}

Is the combination of MEDI5752 with Axitinib or Lenvatinib safe for treating kidney cancer?

The combination of Axitinib or Lenvatinib with immune checkpoint inhibitors like pembrolizumab has been studied for kidney cancer, showing some common side effects such as diarrhea, liver issues, fatigue, and heart-related problems. These side effects require careful management, but the treatments are generally considered safe with proper monitoring. ^{1 4 6 7 8}

Is the drug combination of Axitinib, Lenvatinib, and MEDI5752 promising for kidney cancer?

Yes, the combination of these drugs is promising for kidney cancer. Studies show that combining drugs like Axitinib and Lenvatinib with immune therapies can improve survival and treatment response in kidney cancer patients. These combinations are recommended as first-line treatments for advanced kidney cancer. ^{1 4 5 7 9}

What makes the drug combination of MEDI5752, Axitinib, and Lenvatinib unique for kidney cancer?

The combination of MEDI5752, Axitinib, and Lenvatinib is unique because it includes MEDI5752, a bispecific antibody targeting both PD-1 and CTLA-4, which may enhance the immune response against cancer cells. This approach differs from other treatments that typically use single immune checkpoint inhibitors combined with tyrosine kinase inhibitors, potentially offering a novel mechanism to overcome drug resistance and improve treatment durability. ^{1 4 5 7 9}

What is the purpose of this trial?

This trial is testing a new drug called MEDI5752 combined with either Lenvatinib or Axitinib in patients with advanced kidney cancer. The new drug helps the immune system fight the cancer, while the other drugs stop the cancer cells from growing. The goal is to see if this combination is safe and effective. Axitinib is a drug approved for treating advanced kidney cancer.

Research Team

AstraZeneca Early Oncology

Principal Investigator

AstraZeneca

Eligibility Criteria

Adults with advanced renal cell carcinoma who haven't been treated for it yet can join. They need to be in good health overall, have a life expectancy of at least 12 weeks, and tumors that can be measured. Women must not be pregnant and use birth control; men should too. No recent vaccines or major surgeries, no uncontrolled illnesses or high blood pressure, and no history of certain other cancers or immune disorders.

Inclusion Criteria

You need to have at least one specific spot that can be measured to see how the treatment is working.

You are expected to live for at least 12 more weeks.

My organs and bone marrow are working well.

Exclusion Criteria

I have not taken immunosuppressive medication in the last 14 days.

Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s)

I have been treated with specific immune system drugs for kidney cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Evaluate the safety and tolerability of MEDI5752 in combination with Axitinib and Lenvatinib

3 weeks

Multiple visits as per protocol

Dose Expansion

Evaluate safety and anti-tumor activity of MEDI5752 in combination with Lenvatinib

Up to 48 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days post last dose

Treatment Details

Interventions

• Axitinib
• Lenvatinib
• MEDI5752

Trial Overview The trial is testing MEDI5752 combined with either Lenvatinib or Axitinib on people with kidney cancer to see how well they work together. Participants will receive these medications and their effects will be monitored closely throughout the study period.

Participant Groups

Group I: Dose Exploration Experimental Treatment 3 Interventions

The Dose exploration Phase is made up of Part A, B and Part C. Part A will evaluate the safety and tolerability of MEDI5752 in combination with Axitinib (2 patients), and Part B and C will evaluate the safety and tolerability of MEDI5752 in combination with Lenvatinib (\~72 patients)

Group II: Dose Expansion Experimental Treatment 3 Interventions

Evaluate safety and anti-tumor activity of MEDI5752 in combination with Lenvatinib (\~105 patients )

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

MedImmune LLC

Lead Sponsor

Trials

348

Recruited

788,000+

Founded

1988

Headquarters

Gaithersburg, USA

Known For

Biologics research

Top Products

Synagis, FluMist

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University

Findings from Research

The combination of axitinib and pembrolizumab is tolerable and shows promising antitumor activity in patients with treatment-naive advanced renal cell carcinoma, with 73% of patients achieving an objective response.

In a study involving 52 patients, no unexpected toxicities were observed, although 65% experienced grade 3 or worse treatment-related adverse events, indicating that while the treatment is effective, it does carry some risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Atkins, MB., Plimack, ER., Puzanov, I., et al.[2023]

The combination of avelumab and axitinib significantly improves progression-free survival in patients with advanced renal cell carcinoma by 64% compared to sunitinib.

This drug combination resulted in a response rate of 51% in patients, nearly double the 26% response rate seen with sunitinib, while the incidence of severe side effects (grade 3 or 4) was similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Drug Cocktail Active against RCC. [2019]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

The CLEAR trial showed that the combination of lenvatinib and pembrolizumab significantly improves progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to sunitinib in treatment-naïve metastatic clear-cell renal cell carcinoma.

Combination therapies involving immune checkpoint inhibitors, such as cabozantinib plus nivolumab and axitinib plus pembrolizumab, also demonstrated similar survival benefits and improved quality of life, making them recommended first-line treatments for advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care. Bedke, J., Albiges, L., Capitanio, U., et al.[2022]

Combination therapies using immune checkpoint inhibitors, such as axitinib plus pembrolizumab, have shown improved outcomes compared to traditional sequential monotherapy in patients with metastatic renal cell carcinoma.

Phase III trials indicate that these combination regimens significantly enhance both progression-free survival and overall survival, addressing the issue of drug resistance seen with single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. Spisarová, M., Melichar, B., Vitásková, D., et al.[2021]

Axitinib combined with immune checkpoint inhibitors (ICI) like pembrolizumab or avelumab is now approved for treating advanced renal cell carcinoma, but distinguishing between adverse events (AEs) caused by each treatment is crucial for optimizing therapy.

Experts identified specific AEs such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues that require unique management strategies when using axitinib-ICI combinations, emphasizing the need for careful clinical monitoring and tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Grünwald, V., Voss, MH., Rini, BI., et al.[2021]

In the KEYNOTE-B61 trial involving 158 patients with advanced non-clear-cell renal cell carcinoma, the combination of pembrolizumab and lenvatinib demonstrated a 49% objective response rate, indicating significant antitumor activity as a first-line treatment.

The safety profile was consistent with previous studies, with 51% of patients experiencing grade 3-4 treatment-related adverse events, primarily hypertension, but no deaths were attributed to the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Albiges, L., Gurney, H., Atduev, V., et al.[2023]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

Axitinib demonstrated antitumor activity in patients with metastatic renal cell carcinoma (mRCC) who were refractory to prior therapies, achieving an objective response rate of 22.6% and a median duration of response of 17.5 months in a study of 62 patients.

The treatment was generally well-tolerated, with manageable mild to moderate adverse effects, including hand-foot syndrome and hypertension, indicating that axitinib could be a viable option for patients who have not responded to other VEGF-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. Rini, BI., Wilding, G., Hudes, G., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. [2023]

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

Two-Drug Cocktail Active against RCC. [2019]

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

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care. [2022]

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

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]

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

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. [2023]

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

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. [2018]