BDTX-1535 + Temozolomide for Glioblastoma and Lung Cancer

Not currently recruiting at 89 trial locations

Overseen By BDTX Clinical Trial Navigation Service

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Black Diamond Therapeutics, Inc.

Must be taking: EGFR TKIs

Disqualifiers: Resistant mutations, Interstitial lung disease, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BDTX-1535, to evaluate its safety and effectiveness in treating certain types of lung cancer and brain cancer (glioblastoma). It specifically targets lung cancer patients with specific changes in the EGFR gene, which can cause resistance to standard treatments. The trial includes three groups: those who have tried some treatments, those with a specific mutation, and those who haven't received treatment yet. People with advanced lung cancer and these genetic changes might be suitable for this trial. Participants will take the study drug orally in 21-day cycles to determine if it helps stop cancer growth. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that ongoing or recent anticancer therapy or radiation therapy is an exclusion criterion, which might imply that certain treatments could need to be paused. It's best to discuss your specific medications with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BDTX-1535 was safe and well-tolerated in earlier studies. For example, in a study involving patients with glioblastoma (GBM), most participants did not experience severe side effects. BDTX-1535 is a targeted drug that blocks specific proteins aiding cancer growth, potentially leading to fewer side effects compared to more general treatments.

As this trial is in an early phase, some safety information is available, but more data is needed to confirm these results. If BDTX-1535 receives approval for another condition, it would further support its safety, though that information is not yet available. Overall, the early results are promising for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about BDTX-1535 for glioblastoma and lung cancer because it targets specific EGFR mutations that current treatments, like third-generation EGFR inhibitors such as osimertinib, may not effectively address. BDTX-1535 is designed to work on non-classical and acquired resistance EGFR mutations, which are challenging for existing therapies. This targeted approach could lead to better outcomes for patients with these specific mutations, offering a new hope where current options are limited.

What evidence suggests that this trial's treatments could be effective for glioblastoma and lung cancer?

Research has shown that BDTX-1535, a treatment in this trial, may help treat non-small cell lung cancer (NSCLC) with specific EGFR gene changes. Studies highlight its ability to effectively target both common and less common gene changes. It is also designed to reach the brain, which is crucial for treating cancer that may spread there. For glioblastoma, a severe brain cancer, BDTX-1535 targets specific EGFR changes found in this disease. Early data indicate it reaches the necessary levels in tumors and is well-tolerated by patients, suggesting it could effectively manage these cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Black Diamond Therapeutics

Principal Investigator

Black Diamond Therapeutics

Are You a Good Fit for This Trial?

Adults with advanced lung cancer (NSCLC) having specific EGFR mutations or glioblastoma (GBM) expressing EGFR alterations can join. They must have measurable disease, completed standard treatments like surgery and chemotherapy, and be in stable condition post-treatment. Not eligible if they have certain resistant mutations, brain complications needing urgent care, active hepatitis B/C or HIV, recent major surgery, ongoing cancer therapy other than for NSCLC/GBM.

Inclusion Criteria

For the initial phase, participants must have a disease that can be evaluated. In the later phase, only participants with a measurable disease can join.

My lung cancer is non-small cell type without any small cell transformation.

My cancer has returned after surgery, radiation, or chemotherapy.

Exclusion Criteria

I need urgent treatment for brain or spinal cord issues due to cancer.

I am currently receiving or have recently received cancer treatment.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose(s) of BDTX-1535

21 days

Cycle 1

Phase 2 Treatment

Evaluate the safety, pharmacokinetics, CNS activity, and antitumor activity of BDTX-1535 in multiple cohorts

Approximately 1 year

Every 2 cycles starting on Cycle 3 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BDTX-1535

Trial Overview BDTX-1535 is being tested both alone and combined with temozolomide to see its safety and effectiveness against lung cancer and glioblastoma with EGFR mutations. Patients will take the drug(s) in cycles of 21 or 28 days to assess how well it works on tumors including those spread to the brain.

How Is the Trial Designed?

Group I: Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations Experimental Treatment 1 Intervention

Treatment-naïve (first-line) advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted). Patients with co-occurring L858R mutations and a non-classical mutation are eligible for inclusion.

Group II: Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation Experimental Treatment 1 Intervention

Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only 1 EGFR targeted regimen, which must be a third generation EGFR TKI (eg, osimertinib)

Group III: Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations Experimental Treatment 1 Intervention

Advanced/metastatic NSCLC with a non-classical driver EGFR mutation following up to 2 lines of therapy with only 1 prior EGFR targeted regimen (third-generation preferred; other approved EGFR inhibitors acceptable)

Group IV: Phase 1 Dose Escalation - Monotherapy (Recruitment Closed) Experimental Treatment 1 Intervention

* Advanced/metastatic NSCLC with acquired resistance EGFR mutation (eg, C797S), following a 3rd generation EGFR inhibitor in the 1st line setting (in the absence of concurrent T790M). * Advanced/metastatic NSCLC with non-classical EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor * Recurrent GBM with confirmed EGFR alterations (including amplification, mutation, and/or variant)

Who Is Running the Clinical Trial?

Black Diamond Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

390+

Published Research Related to This Trial

In a phase II trial involving 33 patients with recurrent malignant glioma, the combination of cisplatin and temozolomide showed a progression-free survival (PFS) rate of 52% at 6 months, indicating a potential benefit for patients with this aggressive cancer.

The treatment resulted in partial responses in 18.8% of patients and stable disease in 39.9%, but also led to significant toxic effects, including severe neutropenia and thrombocytopenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients. Silvani, A., Eoli, M., Salmaggi, A., et al.[2022]

In a randomized trial involving 144 patients with anaplastic astrocytoma (AA) and glioblastoma (GBM), neoadjuvant temozolomide (NeoTMZ) did not show a survival advantage for the overall population or for GBM patients compared to radiotherapy alone.

However, patients with AA who received NeoTMZ had a significantly longer median survival of 95.1 months compared to 35.2 months for those receiving only radiotherapy, indicating a potential benefit of NeoTMZ specifically for AA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. Malmström, A., Poulsen, HS., Grønberg, BH., et al.[2018]

In a study of 32 patients with brain metastases from solid tumors, the combination of temozolomide (TMZ) and cisplatin (CDDP) showed promising efficacy, with a 28.1% partial response rate and a median overall survival of 5.5 months.

The treatment was generally well-tolerated, although some patients experienced grade III-IV toxicities, including anemia and leukopenia, indicating that while the regimen is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. Christodoulou, C., Bafaloukos, D., Linardou, H., et al.[2018]

A dual drug-loaded nanoparticle system combining Paclitaxel (PTX) and Temozolomide (TMZ) was developed, showing sustained release and optimal efficacy against glioblastoma cells, particularly at specific weight ratios of PTX to TMZ (1:5 for U87 cells and 1:100 for C6 cells).

In vivo studies demonstrated that PTX/TMZ nanoparticles significantly inhibited tumor growth in a subcutaneous U87 mouse model, indicating that this coordinated drug delivery approach enhances chemotherapy effectiveness for glioblastoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The synergic antitumor effects of paclitaxel and temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells. Xu, Y., Shen, M., Li, Y., et al.[2018]

Depatuxizumab mafodotin (depatux-m) has an acceptable safety profile, with ocular toxicities being the most common side effects observed in 92% of patients, and a maximum tolerated dose of 1.5 mg/kg established for its combination with temozolomide.

In patients with recurrent glioblastoma, depatux-m showed promising preliminary efficacy, with a 6-month progression-free survival rate of 30.8% and a median overall survival of 10.7 months, indicating potential benefits for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Gan, HK., Reardon, DA., Lassman, AB., et al.[2023]

In a phase II study involving 30 patients with brain metastases from non-small cell lung cancer (NSCLC), temozolomide (TMZ) was found to be an active and safe treatment option, with 10% of patients achieving an objective response, including two complete remissions.

No severe (grade 3 or 4) toxicities were reported, and all treatment-related adverse events were mild to moderate, indicating that TMZ can be administered without significant safety concerns in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Giorgio, CG., Giuffrida, D., Pappalardo, A., et al.[2018]

In a study of 85 patients with newly diagnosed glioblastoma, the dose-dense regimen of temozolomide resulted in an impressive 1-year survival rate of 80%, compared to 69% for the metronomic regimen, suggesting it may be a more effective treatment option.

Both treatment regimens were well tolerated with manageable side effects, primarily myelosuppression and elevated liver enzymes, indicating that they are safe options for patients undergoing adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. Clarke, JL., Iwamoto, FM., Sul, J., et al.[2022]

In a phase 1 clinical trial involving 55 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of irinotecan (CPT-11) was found to be 120 mg/m² when combined with temozolomide (TMZ) and O(6)-benzylguanine (O(6)-BG) in patients using enzyme-inducing antiepileptic drugs (EIAEDs).

The study identified significant hematologic toxicities, such as grade 4 neutropenia and thrombocytopenia, as dose-limiting factors, highlighting the need for careful monitoring in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Quinn, JA., Jiang, SX., Reardon, DA., et al.[2021]

Citations

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

Phase 1 study of BDTX-1535, an oral 4th generation ... BDTX-1535 is an oral, highly potent, brain penetrant, selective, irreversible 4 th generation tyrosine kinase inhibitor that targets EGFR alterations in GBM ...

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

Press Release Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) ...

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

Neuro-Oncology | Oxford Academic Recurrent GBM patients with EGFR alterations received BDTX-1535 for 5 days at 200 mg daily (cohort 1) or 400 mg every other day x 3 doses ( ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11485620/

OS06.9.A A PHASE 0/1 'TRIGGER' TRIAL OF BDTX-1535 ... CONCLUSIONS. BDTX-1535 is well-tolerated in recurrent GBM patients, achieves pharmacologically relevant concentrations in Gd non-enhancing tumor tissue and is ...

6. jto.org jto.org/article/S1556-0864(24)02116-6/fulltext

EP.12H.01 A Phase 2 Study to Assess BDTX-1535, An Oral ... BDTX-1535 is a fourth-generation oral, brain-penetrant small molecule inhibitor of oncogenic EGFR classical driver mutations, non-classical driver mutations, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1556086424021166

EP.12H.01 A Phase 2 Study to Assess BDTX-1535, An Oral ... EP.12H.01 A Phase 2 Study to Assess BDTX-1535, An Oral EGFR Inhibitor, in Patients with Non-Small Cell Lung Cancer.

8. onclive.com onclive.com/view/bdtx-1535-generates-early-signals-of-antitumor-activity-in-r-r-egfr-nsclc

BDTX-1535 Generates Early Signals of Antitumor Activity ... BDTX-1535 yielded durable clinical activity in patients with relapsed/refractory, EGFR-mutant NSCLC harboring resistance mutations.