GSK5764227 for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must not be taking: Antibiotics, Immunosuppressants, Monoclonal antibodies, others

Disqualifiers: Infections, Hypertension, Cardiovascular disorders, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GSK5764227, an experimental therapy targeting aggressive brain tumors like glioblastoma and brain metastases. The trial aims to evaluate the treatment's effectiveness and behavior in the body. Participants may advance to a more intensive trial phase if their tumors respond positively to the drug initially. Suitable participants include those with recurrent glioblastoma after standard treatments or brain metastases requiring surgery. As an Early Phase 1 trial, this research seeks to understand the treatment's effects in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study drug. Specifically, you must not have taken any investigational agents, cytotoxic chemotherapy, anticancer drugs, monoclonal antibodies, or immunosuppressive agents within a specified period before the first infusion. Additionally, you should not be on strong/moderate inhibitors of certain enzymes and proteins within 7 days prior to the first infusion. Please consult with the study team for specific guidance on your current medications.

Is there any evidence suggesting that GSK5764227 is likely to be safe for humans?

Research has shown that GSK5764227, a treatment targeting cancer cells, is generally well-tolerated in studies for various advanced cancers. In ongoing research with over 200 participants who have advanced solid tumors, the treatment has demonstrated a promising safety profile, meaning most participants did not experience severe side effects.

The FDA has recognized GSK5764227 by granting it special status for conditions like bone cancer (osteosarcoma) and a type of lung cancer. This recognition suggests that the treatment has shown positive effects, often including reasonable safety.

Although this specific trial is in its early stages, existing evidence provides some reassurance about the treatment's safety. Early trials focus on finding the best dose and monitoring side effects. For those considering joining the trial, this indicates that the treatment has been deemed safe enough for human testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

GSK5764227 is unique because it offers a new approach to treating glioblastoma, a particularly aggressive brain cancer. Unlike traditional treatments that typically involve surgery, radiation, and chemotherapy, GSK5764227 is designed to target specific molecular pathways involved in tumor growth. This targeted action means it could potentially be more effective and have fewer side effects compared to conventional options. Researchers are excited about its potential to provide a more precise attack on cancer cells, which might lead to better outcomes for patients with recurrent glioblastoma and those with brain metastases.

What evidence suggests that GSK5764227 might be an effective treatment for glioblastoma?

Research shows that GSK5764227, an antibody-drug conjugate (ADC), may help treat certain cancers. In studies for conditions like extensive-stage small cell lung cancer, this treatment controlled the disease in 81.8% of patients. Specifically, over 80% of patients did not experience cancer progression during the study. On average, the treatment halted cancer growth for about 4.7 months. In this trial, participants with recurrent glioblastoma (Arm A) or brain metastases (Arm B) will receive GSK5764227. GSK5764227 targets a protein called B7-H3, often found in large amounts on cancer cells, which could help kill cancer cells and offer hope for people with glioblastoma or brain metastases. ^{1 6 7 8 9}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

This trial is for about 15 people with recurrent Grade 4 glioma or brain metastases. Participants must show a positive response in the initial phase to continue to the therapeutic dosing phase.

Inclusion Criteria

For females of non-childbearing potential: Is no longer of childbearing potential

Able and willing to comply with scheduled visits, treatment plans, and procedures

Understands the informed consent document and has voluntarily agreed to participate

Exclusion Criteria

Unable to undergo MRI of the brain with IV contrast

Known other concurrent severe psychiatric and/or uncontrolled medical condition

I have not had serious infections in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Phase 0

Participants with rGBM and brain metastases receive investigational drug GSK5764227 to determine optimal time interval for surgery based on PK data

8 weeks

Multiple visits for infusion and surgery

Phase 1

Participants with positive PK response continue GSK5764227 treatment every three weeks until disease progression or other criteria are met

Variable, based on individual response

Infusions every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including 30-day, 60-day, and 90-day safety follow-up visits

3 months

3 visits (in-person)

Long-term Follow-up

Participants are monitored for survival and disease progression with MRI scans and RANO reviews every 2-3 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• GSK5764227

Trial Overview The study tests GSK5764227, an antibody-drug conjugate targeting B7-H3, on patients with specific types of brain cancer. It includes an early Phase 0 to check drug behavior and a later Phase 1 for those responding well.

How Is the Trial Designed?

Group I: Arm B (Brain Mets) Experimental Treatment 1 Intervention

Participants with brain metastases

Group II: Arm A (rGBM) Experimental Treatment 1 Intervention

Participants with recurrent WHO Grade 4 glioma (rGBM)

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07268053?term=glioblastoma

Study Details | NCT07268053 | A Phase 0/1 Clinical Trial ... This will be an open-label Phase 0/1 study that will enroll approximately 15 participants, 9 participants with recurrent WHO Grade 4 glioma ...

2. onclive.com onclive.com/view/fda-grants-btd-to-gsk5764227-for-extensive-stage-small-cell-lung-cancer

FDA Grants BTD to GSK5764227 for Extensive-Stage ... The disease control rate (DCR) was 81.8% (95% CI, 48.2%-97.7%). Moreover, the median progression-free survival (PFS) was 4.7 months (95% CI, 1.4 ...

3. cancernetwork.com cancernetwork.com/view/novel-drug-receives-fda-breakthrough-therapy-designation-for-r-r-osteosarcoma

Novel Drug Receives FDA Breakthrough Therapy ... GSK5764227 yielded promising antitumor efficacy while showing no new safety signals in patients with relapsed/refractory osteosarcoma, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06885034

NCT06885034 | A Study to Test the Safety and ... This study will check how well a new medicine, GSK5764227, works, how safe it is and how the body handles it in participants all around the world with ...

5. targetedonc.com targetedonc.com/view/fda-grants-b7-h3-targeted-adc-breakthrough-status-in-osteosarcoma

FDA Grants B7-H3–Targeted ADC Breakthrough Status in ... The FDA has granted BTD to GSK'227, a B7-H3-targeted ADC being evaluated for the treatment of adult patients with relapsed/refractory osteosarcoma.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06551142

NCT06551142 | A Study of GSK5764227 in Participants ... The goal of this study is to assess the safety, tolerability, clinical activity and pharmacokinetics of GSK5764227. The study will also see how the levels ...

7. trial.medpath.com trial.medpath.com/clinical-trial/e8bb14330bb74c8a/nct07268053-gsk5764227-b7h3-adc-recurrent-glioma-brain-metastases

A Phase 0/1 Clinical Trial With an Expansion ... - MedPath All participants will return to the clinic for safety monitoring per the schedule of activities following GSK5764227 treatment discontinuation, ...

8. targetedonc.com targetedonc.com/view/gsk5764227-gains-fda-breakthrough-therapy-designation-in-es-sclc

GSK5764227 Gains FDA Breakthrough Therapy ... The FDA has granted GSK5764227 a breakthrough therapy designation for the treatment of extensive-stage small cell lung cancer.

9. ctv.veeva.com ctv.veeva.com/study/a-study-to-test-the-safety-and-effectiveness-of-gsk5764227-alone-or-with-other-treatments-in-parti

A Study to Test the Safety and Effectiveness of GSK5764227 ... This study will check how well a new medicine, GSK5764227, works, how safe it is and how the body handles it in participants all around the world with advanced ...