What side effects are associated with this type of intervention?

Common treatments for kidney cancer, such as tyrosine kinase inhibitors (TKIs) like Lenvatinib and Axitinib, often cause side effects including hypertension, diarrhea, fatigue, hand-foot syndrome, and liver toxicity. When combined with immunotherapy agents, additional immune-related adverse events can occur, such as colitis, pneumonitis, hepatitis, and endocrinopathies. Patients undergoing these combination therapies should be closely monitored for both TKI-related and immune-related toxicities.

What prior FDA approvals exist?

Lenvatinib and Axitinib, both tyrosine kinase inhibitors, have received FDA approval for the treatment of advanced renal cell carcinoma. Lenvatinib is often used in combination with pembrolizumab, showing significant improvements in progression-free survival and overall response rates. Axitinib is commonly combined with avelumab or pembrolizumab, aiming to enhance anti-tumor activity by targeting multiple pathways. These combinations are designed to improve treatment outcomes by leveraging the synergistic effects of TKIs and immunotherapy.

What other types of research exist?

Promising alternatives to MEDI5752 in combination with Lenvatinib or Axitinib for kidney cancer patients include: 1) Nivolumab plus Ipilimumab, which has shown durable long-term responses and the potential for treatment-free intervals. 2) Atezolizumab plus Bevacizumab, which has demonstrated efficacy in patients with metastatic renal cell carcinoma. 3) Cabozantinib, which has been effective after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma. These alternatives offer different mechanisms of action and potential benefits for patients.

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Tyrosine Kinase Inhibitor

MEDI5752 + Axitinib/Lenvatinib for Kidney Cancer

Phase 1

Recruiting

Research Sponsored by MedImmune LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or fresh tissue sample

Age ≥ 18 at the time of screening

Must not have

Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitor

Previous treatment with VEGF inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up informed consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include high blood pressure, fatigue, diarrhea, loss of appetite, weight changes, nausea, mouth sores, rash or redness of the skin. There may also be risks related to liver function changes and potential bleeding issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can provide at least 5 slides or a tissue block from my tumor.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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I weigh more than 35 kilograms.

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My advanced kidney cancer has not been treated yet.

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My kidney cancer is confirmed and has clear cell features.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have been treated with VEGF inhibitors before.

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My blood pressure is high (≥ 140/90 mmHg) and hasn't been controlled before starting treatment.

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I have had an organ transplant.

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I have had significant coughing up of blood or tumor bleeding in the last 2 weeks.

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I have not had a blood clot in the last 6 months.

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I have a serious wound, ulcer, or bone fracture that won't heal.

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I still have side effects from past cancer treatments.

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My cancer has spread to major blood vessels.

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I do not have active infections like TB, HIV, or hepatitis B/C.

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I have or had an autoimmune or inflammatory disorder.

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I have a major issue with my digestive system.

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I have a heart rhythm problem that is noticeable, treated, or not controlled.

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I haven't had major surgery or radiation in the last 4 and 2 weeks, respectively, and have recovered from any side effects.

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I have had another type of cancer.

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My cancer has spread to my brain or spinal cord and is either untreated or getting worse.

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I am not currently receiving any treatment for cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ informed consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~informed consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first

This trial's timeline: 3 weeks for screening, Varies for treatment, and informed consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Dose Limiting Toxicities (DLT) of MEDI5752 and Lenvatinib (or Axitinib) during the Dose Exploration period.

Number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events.

Number of subjects experiencing abnormal laboratory evaluations.

+4 more

Secondary study objectives

Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Best Overall Response (BOR) according to RECIST v1.1.

Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Disease Control Rate (DCR).

Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Duration of Response (DOR) according to RECIST v1.1.

+8 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose ExplorationExperimental Treatment3 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 ExpansionExperimental Treatment3 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Axitinib

2020

Completed Phase 2

~3050

Lenvatinib

2017

Completed Phase 4

~2040

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney cancer, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (TKIs), work by targeting specific mechanisms involved in cancer progression. Immune checkpoint inhibitors, like the investigational drug MEDI5752, enhance the immune system's ability to recognize and destroy cancer cells. TKIs, such as Lenvatinib and Axitinib, block enzymes that promote cancer cell growth and spread. These mechanisms are crucial for kidney cancer patients as they offer targeted approaches to inhibit tumor growth and improve treatment outcomes.

An evidence-based guide to the selection of sequential therapies in metastatic renal cell carcinoma.