What side effects are associated with this type of intervention?

Common treatments for Glioblastoma, particularly those involving PD-1 inhibitors like Cemiplimab, often result in immune-related side effects such as fatigue, rash, diarrhea, and endocrine disorders like hypothyroidism. Investigational drugs similar to ASP8374 may present additional side effects, including nausea, fatigue, and blood-related abnormalities. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including the PD-1 inhibitor nivolumab, which is similar to cemiplimab. Nivolumab is used to enhance the immune system's ability to fight cancer cells. Additionally, bevacizumab, an anti-VEGF antibody, has been approved for recurrent Glioblastoma to inhibit tumor blood vessel growth. Temozolomide, an oral alkylating agent, is also commonly used in combination with radiotherapy for newly diagnosed Glioblastoma. These treatments aim to target the tumor through various mechanisms, including immune modulation and inhibition of angiogenesis.

What other types of research exist?

Promising alternatives for glioblastoma treatment in 2024 include: 1) Nivolumab (another PD-1 inhibitor) combined with ipilimumab (CTLA-4 inhibitor), 2) Tumor Treating Fields (TTFields) therapy, 3) CAR T-cell therapies targeting EGFRvIII, and 4) Oncolytic virus therapies such as DNX-2401. These therapies are in various stages of clinical trials and show potential in improving outcomes for glioblastoma patients.

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Monoclonal Antibodies

ASP8374 + Cemiplimab for Recurrent Brain Cancer

Phase 1

Waitlist Available

Led By David A Reardon, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

At first or second relapse

Previous first line therapy with at least radiotherapy

Must not have

Known history of active TB

Diagnosis of immunodeficiency

Timeline

Screening 3 weeks

Treatment Varies

Follow Up enrollment up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety and effectiveness of combining two drugs, ASP8374 and cemiplimab, for people with recurrent brain cancer. The study aims to find the best dose and see if the combination helps before surgery. The drugs work by boosting the immune system to fight cancer cells. Cemiplimab has been previously tested in combination with other treatments for severe cancers.

Who is the study for?

This trial is for adults over 18 with recurrent malignant glioma, either WHO grade IV GBM or variants, or grade III (Cohort 1 only). They must have a Karnofsky performance status of ≥70 and show tumor progression. Participants need adequate organ function and should be at their first or second relapse after radiotherapy. Pregnant women and those with certain medical conditions or treatments are excluded.

What is being tested?

The study tests the combination of ASP8374 with cemiplimab in two parts: finding the safest high dose (Part 1) and assessing its effect before surgery (Part 2). It aims to establish safety and effectiveness against recurrent brain tumors.

What are the potential side effects?

While specific side effects aren't listed, similar trials often involve risks like immune reactions, inflammation in various organs, fatigue, allergic responses to drug components, infection risk increase due to immunosuppression, bleeding complications, and potential interference with other medications.

Eligibility Criteria

Inclusion Criteria

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

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My condition has worsened for the first or second time after improving.

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I have received radiotherapy as my first treatment.

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I am 18 years old or older.

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I am able to care for myself but may not be able to do active work.

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I am not pregnant.

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My organs are functioning well.

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My brain tumor is confirmed to be a high-grade glioma.

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I am mostly able to care for myself and carry out daily activities.

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I have received radiotherapy as my first treatment.

Exclusion Criteria

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

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I have an active tuberculosis infection.

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I have been diagnosed with an immune system disorder.

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My tumor is mainly in my brainstem or spinal cord.

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I am currently on medication for an infection.

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I haven't had severe bleeding in the last 6 months.

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I have a confirmed case of non-infectious lung inflammation.

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I have been diagnosed with HIV.

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I need to take a moderate or high dose of steroids within a week of signing up.

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I have not needed treatment for an autoimmune disease in the last 2 years.

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I have been treated with drugs targeting VEGF or VEGFR.

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My cancer has spread to the lining of my brain or other parts of my body.

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I have not taken drugs to suppress my immune system in the last 6 months.

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I have an active Hepatitis B or C infection.

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I have been treated with the drug idelalisib before.

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I have been treated with specific immune-targeting drugs before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ enrollment up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~enrollment up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and enrollment up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

CD8+ TIL Tumor Density-Cohort 2

Maxium Tolerated Dose-MTD/ Phase 2 Recommend Dose-RP2D - Cohort 1

Secondary study objectives

Rate of Adverse Events

overall survival (OS).

progression-free survival (PFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: ASP8374 and Cemiplimab-Cohort 2Experimental Treatment2 Interventions

Upon determination of the MTD/RP2D of ASP8374 plus cemiplimab in Cohort 1, a dose expansion will be performed in which eligible participants who are candidates for surgical resection will enroll to Cohort 2 and will be randomized into one of two treatment groups (2A-2B). Group 2A: IV ASP8374 plus cemiplimab within 14± 5 days prior to surgery at the MTD/RP2D established in Cohort 1. Group 2B: No immune checkpoint therapy prior to surgery. Post-operatively, all Cohort 2 participants will receive ASP8374 plus cemiplimab every 3 weeks administered at the MTD/RP2D established by Cohort 1

Group II: ASP8374 and Cemiplimab-Cohort 1Experimental Treatment2 Interventions

A 3+3 dose escalation design will be used to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when combined with cemiplimab. Participants will receive ASP8374 and Cemiplimab every 3 weeks for up to 2 years. ASP8374 will be available until October 31, 2022. Subjects may continue treatment with cemiplimab alone after that date.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ASP8374

2017

Completed Phase 1

~180

cemiplimab

2016

Completed Phase 2

~910

0 / 24Eligibility 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

Glioblastoma treatments often include a combination of surgery, radiation, and chemotherapy. Targeted therapies, like ASP8374, aim to interfere with specific molecules involved in tumor growth and progression, though the exact mechanism of ASP8374 is not yet known. Immune checkpoint inhibitors, such as Cemiplimab, work by blocking the PD-1 pathway, which tumors use to evade the immune system. By inhibiting PD-1, Cemiplimab helps the immune system recognize and attack cancer cells. These treatments are crucial for Glioblastoma patients as they offer potential for more effective and personalized therapy options, improving outcomes and survival rates.