MEDI5752 + Axitinib/Lenvatinib for Kidney Cancer

Not currently recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced kidney cancer. Researchers are examining how well the experimental drug MEDI5752 works when combined with either Lenvatinib or Axitinib. The goal is to determine if this combination is safe and can shrink tumors in patients who haven't received similar treatments before. Individuals diagnosed with advanced kidney cancer, specifically with a clear cell component, and who have not yet received treatment, might be suitable for this study. 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.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that MEDI5752, when used alone, has strong effects against advanced kidney cancer. However, safety concerns exist. In past studies, 71.2% of patients experienced serious side effects, and 14.4% discontinued treatment due to these effects. Fatal side effects were rare, occurring in only 1% of patients.

Axitinib, another drug in the trial, has been studied before and is approved for treating kidney cancer when other treatments fail. This suggests relative safety, but it can still cause side effects like diarrhea, high blood pressure, and tiredness.

Lenvatinib, also part of the trial, is used for treating other types of cancer. It is generally well-tolerated but can lead to side effects such as high blood pressure and fatigue.

In this trial, researchers are studying the effectiveness and safety of these drugs in combination. As an early-phase trial, the main focus is on assessing safety and tolerability. While promising data exists, considering potential side effects is important before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of MEDI5752 with Axitinib and Lenvatinib for kidney cancer because it introduces a novel approach to treatment. Unlike traditional therapies that primarily target blood vessel growth in tumors, MEDI5752 is a unique bispecific antibody that simultaneously targets two immune checkpoints, potentially enhancing the immune system's response against cancer cells. This dual action could lead to improved anti-tumor activity. Additionally, combining MEDI5752 with established drugs like Axitinib and Lenvatinib, which are already known for inhibiting tumor blood vessel growth, might offer a more comprehensive attack on cancer cells, possibly leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that MEDI5752, when combined with Axitinib, yields promising results for treating kidney cancer. In some studies, this combination achieved a 58% overall response rate, with more than half of the patients experiencing tumor shrinkage. Fewer than 10% of patients saw their condition worsen during the trial. In this trial, some participants will receive the combination of MEDI5752 and Axitinib.

Additionally, MEDI5752 alone has demonstrated strong effects against tumors, even in challenging cases of kidney cancer. When combined with Lenvatinib, MEDI5752 also resulted in significant tumor shrinkage. Other participants in this trial will receive the combination of MEDI5752 and Lenvatinib. These findings suggest that these combination treatments could effectively manage advanced kidney cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

AstraZeneca Early Oncology

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)01950-6/pdf

1883MO MEDI5752 (volrustomig), a novel PD-1/ ... Conclusions: Among patients with previously untreated advanced RCC, treatment with toripalimab plus axitinib resulted in significantly longer PFS, as well as a ...

2. urotoday.com urotoday.com/conference-highlights/esmo-2023/esmo-2023-kidney-cancer/147556-esmo-2023-medi5752-volrustomig-a-novel-pd-1-ctla-4-bispecific-antibody-in-the-first-line-1l-treatment-of-65-patients-pts-with-advanced-clear-cell-renal-cell-carcinoma-arcc.html

ESMO 2023: MEDI5752 (Volrustomig), a Novel PD-1/CTLA ... In the 1st line ccRCC setting, 1,500 mg administered every 3 weeks has promising efficacy (ORR: 58%, progressive disease <10%), but dosing is ...

3. meetings.asco.org meetings.asco.org/abstracts-presentations/209273

Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 ... MEDI5752 monotherapy showed deep and durable antitumor activity in pts with advanced RCC, despite high rates of treatment D/C, particularly in the 1L setting.

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7980C00003

A Study to Evaluate MEDI5752 and Axitinib in Subjects ... The purpose of this study is to evaluate MEDI5752 in combination with Lenvatinib (or Axitinib), in subjects with advanced renal cell carcinoma.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10836322/

Research Accelerating Cures for Renal Cell Carcinoma in 2023 This commentary summarizes the most important emerging areas of kidney cancer research discussed and debated among the stakeholders at the conference.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04522323

NCT04522323 | A Study to Evaluate MEDI5752 and ... The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of MEDI5752 in combination ...

7. inlyta.com inlyta.com/axitinib/clinical-trial-results

INLYTA® (axitinib) Clinical Trial Results | Safety Info Find clinical trial results for INLYTA® (axitinib), an Rx option for advanced RCC when 1 prior drug treatment regimen has not worked. See risks & benefits.