BDTX-1535 + Temozolomide for Glioblastoma and Lung Cancer

Recruiting at 81 trial locations

Overseen By BDTX Clinical Trial Navigation Service

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Black Diamond Therapeutics, Inc.

Must be taking: EGFR TKIs

Disqualifiers: Resistant mutations, Interstitial lung disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of BDTX-1535. The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma (GBM) expressing EGFR alterations (Phase 1 only). All patients will self-administer BDTX-1535 monotherapy by mouth in 21-day cycles. Phase 1 enrollment is now complete. Phase 2 is currently enrolling.

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.

What data supports the effectiveness of the drug BDTX-1535 + Temozolomide for Glioblastoma and Lung Cancer?

Research shows that temozolomide, when used with other drugs, can improve outcomes in glioblastoma, a type of brain cancer. For example, combining temozolomide with other treatments has shown to help in slowing tumor growth and improving survival in some studies. ^{1 2 3 4 5}

What makes the drug BDTX-1535 unique for treating glioblastoma and lung cancer?

BDTX-1535 is unique because it is being studied in combination with temozolomide, a standard chemotherapy drug, to potentially enhance its effectiveness against glioblastoma and lung cancer. This combination approach aims to improve treatment outcomes by leveraging the strengths of both drugs. ^{2 5 6 7 8}

Research Team

Black Diamond Therapeutics

Principal Investigator

Black Diamond Therapeutics

Eligibility Criteria

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.

I have recovered from major surgery to remove as much cancer as possible.

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.

Trial Timeline

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

Treatment Details

Interventions

• BDTX-1535 (Small Molecule Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The synergic antitumor effects of paclitaxel and temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells. [2018]

3. United States 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. [2023]

6. England 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. [2018]

7. Ireland pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients. [2022]