BDTX-1535 for Brain Tumor

Recruiting at 1 trial location

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Must not be taking: Prohibited medications

Disqualifiers: Pregnancy, Liver disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Continuous 28-day cycles

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BDTX-1535, for individuals with specific brain tumors, such as recurrent high-grade glioma and newly-diagnosed glioblastoma. The drug targets changes in a protein called EGFR, which contributes to tumor growth. Researchers aim to determine if BDTX-1535 is safe and effective for patients. Those with tumors that have recurred after standard treatments or are newly diagnosed without prior treatment, and whose tumors exhibit specific protein changes, may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial mentions that some medications are prohibited, but it doesn't specify which ones. You may need to stop certain medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that BDTX-1535 is likely to be safe for humans?

Research has shown that BDTX-1535 has a good safety record in earlier studies with patients who have brain tumors. Early results suggest that BDTX-1535 is generally safe and well-tolerated, particularly for those with glioblastoma multiforme (GBM), a type of brain cancer. In these studies, patients experienced manageable side effects that did not cause serious problems or harm.

These findings come from trials examining the drug's function in the body and its safety. The trials demonstrated that BDTX-1535 can be administered safely, which is encouraging for those considering it as a treatment option in clinical trials. Although research is ongoing, the data so far supports its safety for use in people with brain tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and chemotherapy, BDTX-1535 is a targeted therapy that focuses on specific genetic alterations in the tumor. This drug is unique because it targets EGFR alterations, which are common in high-grade gliomas and glioblastomas. By honing in on these specific genetic changes, BDTX-1535 aims to be more precise and potentially more effective than traditional therapies. Researchers are excited because this targeted approach could lead to better outcomes with fewer side effects, making it a promising option for patients with these challenging brain tumors.

What evidence suggests that BDTX-1535 might be an effective treatment for brain tumors?

Research has shown that BDTX-1535 targets a specific change in brain tumors known as EGFR alterations. Early studies indicate that BDTX-1535 can reach potentially effective levels in brain tumor tissue. In this trial, participants with recurrent high-grade glioma or newly-diagnosed GBM will receive BDTX-1535 in different treatment arms. Specifically, some patients with recurring glioblastoma, a type of brain tumor, used BDTX-1535 and maintained stable disease for over five months after other treatments proved ineffective. This suggests that BDTX-1535 might help slow tumor growth in some patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Chief Scientific Officer/Director of the Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent high-grade glioma brain tumors that have progressed after standard treatments, including surgery, temozolomide chemotherapy, and radiotherapy. Participants must have specific EGFR gene changes in their tumors and be able to swallow pills. They should be relatively stable physically (ECOG PS ≤2) and not have severe cardiovascular disease, active infections or liver disease.

Inclusion Criteria

My bone marrow and organs are functioning well.

I had surgery for a high-grade glioma and have received standard treatments but my cancer has progressed.

I can perform all self-care but cannot work.

Exclusion Criteria

I have a serious heart condition.

I do not have severe infections or serious liver diseases.

I have symptoms or imaging results showing disease in the lining of my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants receive BDTX-1535 prior to planned resection; samples collected during surgery

1 week

1 visit (in-person, surgical)

Treatment

Participants with PK response continue with once-daily BDTX-1535 in 28-day cycles

Continuous 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• BDTX-1535

Trial Overview BDTX-1535 is being tested in this study. It's a new drug aimed at blocking a growth signal in cancers linked to certain EGFR protein alterations found only in the tumors. The goal is to see if it can safely help people whose tumors depend on this signal due to these genetic changes.

How Is the Trial Designed?

Group I: Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol) Experimental Treatment 1 Intervention

Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with methylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Participants with methylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT and temozolomide (TMZ), followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group II: Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety) Experimental Treatment 1 Intervention

Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with unmethylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Arm D: Participants with unmethylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group III: Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination) Experimental Treatment 1 Intervention

Phase 0: Participants in Cohort 1 will receive 200 mg of BDTX-1535 once daily for 5 days, and participants in Cohort 2 will receive 150 mg of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. . Participants with unmethylated MGMT promoter tumors demonstrating PK response will proceed to the Phase 1 Expansion component. The OBD will be the lowest dose that achieves the following: 9 of 12 participants show PK response and 6 of 12 participants show PD response. Phase 1: Participants with unmethylated MGMT promoter tumors demonstrating a PK response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group IV: Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion Experimental Treatment 1 Intervention

Phase 0: Participants will received BDTX-1535 once daily (Days 1-5). The dose level will be determined based on PK results from Arm A, unbound drug concentration in non-enhancing tumor. The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Group V: Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations Experimental Treatment 1 Intervention

Phase 0: Cohort 1 will receive 200 mg BDTX-1535 once daily (Days 1-5). Cohort 2 will receive 400 mg BDTX-1535 three times over one week (Days 1, 3, and 5). The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Citations

1. investors.blackdiamondtherapeutics.com investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-presents-promising-bdtx-1535-clinical

Press Release Initial results from the trial demonstrated that BDTX-1535 exceeded the pre-specified threshold for drug concentration in the brain tumor tissue ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT023/761334/Abstract-CT023-A-phase-0-1-trigger-trial-of-BDTX

Abstract CT023: A phase 0/1 'trigger' trial of BDTX-1535 in ... At data cutoff, the median survival was 4.9 months. Conclusions: For recurrent GBM patients, BDTX-1535 achieves pharmacologically relevant ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2068

Phase 1 study of BDTX-1535, an oral 4th generation ... Five patients remained on BDTX-1535 with stable disease for an extended period (>5 months) who previously performed poorly on TMZ with short ...

4. academic.oup.com academic.oup.com/neuro-oncology/article-abstract/27/Supplement_3/iii122/8272049

Neuro-Oncology | Oxford Academic This Phase 0/1 study evaluates the pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcomes of BDTX-1535, an ATP-competitive, ...

5. onclive.com onclive.com/view/dr-sanai-on-the-evaluation-of-bdtx-1535-in-egfr-mutated-high-grade-glioblastoma

Dr Sanai on the Evaluation of BDTX-1535 in EGFR ... In the phase 1 portion, among 8 patients evaluable for safety, 37.5% had any-grade adverse effects (AEs), 25.0% had grade 3 or higher AEs, and ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT06072586

A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade ... This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05256290

Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients ... BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), ...

8. investors.blackdiamondtherapeutics.com investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-reports-first-quarter-2025-financial

Black Diamond Therapeutics Reports First Quarter 2025 ... The data showed encouraging pharmacokinetic and safety data for BDTX-1535 in recurrent EGFR-positive GBM patients, providing a strong ...