What is the mechanism of action of this treatment?

Common treatments for solid tumors, such as immune checkpoint inhibitors targeting PD-1 and CTLA-4, work by blocking the pathways that cancer cells use to evade the immune system. By inhibiting these checkpoints, drugs like MEDI5752 enhance the body's immune response against tumor cells. This mechanism is crucial for solid tumor patients as it can lead to more effective and durable responses, offering a significant advantage over traditional therapies like chemotherapy, which often have limited efficacy and substantial side effects in advanced stages.

What side effects are associated with this type of intervention?

The most common treatments for solid tumors using dual checkpoint inhibitors, such as those targeting PD-1 and CTLA-4, are associated with a range of immune-related adverse events (irAEs). These include colitis, dermatitis, hepatitis, endocrinopathies (such as thyroiditis and adrenal insufficiency), and pneumonitis. High-grade adverse events can occur in up to 60% of patients, requiring vigilant monitoring and management to mitigate these potentially severe side effects.

What prior FDA approvals exist?

The FDA has approved several drugs targeting PD-1 and CTLA-4 for the treatment of solid tumors. Nivolumab (Opdivo) and pembrolizumab (Keytruda) are PD-1 inhibitors approved for various cancers, including non-small cell lung cancer (NSCLC) and melanoma. Ipilimumab (Yervoy) is a CTLA-4 inhibitor approved for melanoma. Combination therapies, such as nivolumab plus ipilimumab, have also been approved for advanced melanoma and NSCLC, demonstrating the efficacy of dual checkpoint inhibition similar to the approach being studied with MEDI5752.

What other types of research exist?

Promising alternatives to MEDI5752 for solid tumors include: 1) Nivolumab plus Ipilimumab, which has shown improved overall survival in various cancers such as melanoma, non-small cell lung cancer, and mesothelioma. 2) Pembrolizumab in combination with other agents like chemotherapy or targeted therapies, which has demonstrated efficacy in multiple solid tumors. 3) Nivolumab plus Relatlimab, a newer combination showing promise in advanced melanoma. These alternatives offer different mechanisms of action and toxicity profiles, allowing for tailored treatment approaches.

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Chemotherapy

MEDI5752 for Solid Cancers

Phase 1

Waitlist Available

Led By Deepa Subramaniam, MD, MSc

Research Sponsored by MedImmune LLC

Eligibility Criteria Checklist

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

Must have

World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment

Histologically or cytologically-confirmed advanced solid tumors

Must not have

Active or prior documented autoimmune or inflammatory disorders

Untreated CNS metastatic disease, leptomeningeal disease, or cord compression

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after the last patient starts treatment, whichever should occur first

Awards & highlights

Summary

This trial is testing a new drug called MEDI5752 along with common chemotherapy drugs in adults with advanced cancer. The goal is to see if MEDI5752 can help fight cancer on its own or when combined with chemotherapy.

Who is the study for?

Adults with advanced solid tumors who have a life expectancy of at least 12 weeks, can provide tumor material, and have adequate organ function. They must not be involved in the study's conduct or enrolled in another clinical trial. Participants need to use effective contraception and cannot have untreated brain metastases, uncontrolled illnesses, or a history of severe autoimmune disorders.

What is being tested?

The trial is testing MEDI5752 alone or combined with chemotherapy drugs like carboplatin and pemetrexed or paclitaxel/nab-paclitaxel. It aims to see how well these treatments work for adults with various types of advanced solid tumors.

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting organs, infusion-related reactions from the drug entering the body, fatigue, digestive issues such as nausea and diarrhea, blood cell count changes leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer is confirmed to be advanced and not just limited to one area.

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I am using a reliable birth control method.

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My organs and bone marrow are working well.

Exclusion Criteria

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

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I have or had an autoimmune or inflammatory disorder.

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I have brain metastases or spinal cord issues that haven't been treated.

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I have had an organ transplant.

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Any side effects from my previous immunotherapy have fully gone away or are mild.

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I haven't taken immunosuppressive drugs in the last 14 days.

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My side effects from previous cancer treatments have mostly gone away.

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I haven't had major surgery or am still recovering from one within the last 28 days.

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I am not pregnant or breastfeeding and willing to use effective birth control.

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I have never stopped an immunotherapy treatment because of severe side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the first dose of study drug 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 ~from the first dose of study drug 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 from the first dose of study drug 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

Preliminary anti-tumor activitiy of MEDI5752 (versus pembrolizumab, where applicable) using Objective Response based on RECIST v1.1 (Dose-expansion phase)

The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events (Dose-escalation phase)

The number of subjects experiencing abnormal laboratory evaluations (Dose-escalation phase)

+4 more

Secondary study objectives

Neoplasms

PD-L1 Expression in subjects with advanced solid tumors

Pharmacokinetics of MEDI5752: AUC

+12 more

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm B: MEDI5752 and chemotherapyExperimental Treatment4 Interventions

MEDI5752, pemetrexed, carboplatin and paclitaxel.

Group II: Arm A: MEDI5752Experimental Treatment1 Intervention

MEDI5752

Group III: Arm C: Pembrolizumab and chemotherapyActive Control3 Interventions

pembrolizumab, pemetrexed, and carboplatin

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Carboplatin

2014

Completed Phase 3

~6120

0 / 13Eligibility 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 solid tumors, such as immune checkpoint inhibitors targeting PD-1 and CTLA-4, work by blocking the pathways that cancer cells use to evade the immune system. By inhibiting these checkpoints, drugs like MEDI5752 enhance the body's immune response against tumor cells. This mechanism is crucial for solid tumor patients as it can lead to more effective and durable responses, offering a significant advantage over traditional therapies like chemotherapy, which often have limited efficacy and substantial side effects in advanced stages.

Expanding Therapeutic Options for Older Adults: Case-Based Updates in Breast and Lung Cancer.Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes.Propelling Immunotherapy Combinations Into the Clinic.