Study of BDTX-1535, in Participants With Glioblastoma or Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
This is a first-in-human, open label, multicenter study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and the preliminary antitumor activity of BDTX-1535 in patients with GBM or NSCLC harboring sensitive EGFR alterations and who have disease progression following standard of care
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
BDTX-1535 is an orally available, highly potent, selective, irreversible inhibitor of allosteric epidermal growth factor receptor (EGFR) alterations, including amplification, mutations, and splice variants which have been identified in glioblastoma (GBM) and mutations in non-small cell lung cancer (NSCLC) associated with intrinsic or acquired resistance. The open label, multicenter will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BDTX-1535 in patients with GBM harboring EGFR alterations and NSCLC with EGFR mutations of intrinsic or acquired resistance who have failed standard treatment. Dose escalation cohorts will be used to determine the maximum tolerated dose and recommended phase 2 dose of BDTX-1535 oral administration
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Monotherapy Dose Escalation Enrolling patients with GBM and NSCLC harboring sensitive EGFR alterations |
Drug: BDTX-1535 Monotherapy Dose Escalation
Participants will receive a daily, oral dose of BDTX-1535 as part of a 21-day cycle. Subsequent cohorts will test increasing doses of BDTX-1535 until a maximum tolerated dose or a recommended phase 2 dose is defined.
|
| Experimental: Disease-Specific Dose Expansion Cohorts Recurrent GBM with confirmed EGFR alterations NSCLC with uncommon EGFR mutations (eg, G719X), following standard of care therapy with an EGFR inhibitor 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) |
Drug: BDTX-1535 Monotherapy
Participants will receive a daily, oral dose of BDTX-1535 at the recommended phase 2 dose as part of a 21-day cycle.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with dose limiting toxicities (DLTs) [From first dose of study treatment until the end of Cycle 1 (approximately 21 days)]
DLTs are based on drug-related adverse events, including pre-defined hematological and non-hematological toxicities, that occur from the first dose of study treatment through the end of Cycle 1
Secondary Outcome Measures
- Number of participants with treatment-emergent adverse events [Up to approximately 3 years]
An AE is any untoward medical occurrence in a participant who receives study treatment, which does not necessarily have a causal relationship with the treatment
- Maximum plasma concentration (Cmax) of BDTX-1535 [Up to approximately 3 years]
Cmax is calculated to characterize the pharmacokinetic properties of study treatment
- Time to maximum plasma concentration (Tmax) of BDTX-1535 [Up to approximately 3 years]
Tmax is calculated to characterize the pharmacokinetic properties of study treatment
- Area under the plasma concentration-time curve (AUC) of BDTX-1535 [Up to approximately 3 years]
AUC is calculated to characterize the pharmacokinetic properties of study treatment
- Objective Response Rate (ORR) [Up to approximately 3 years]
ORR is the percentage of participants who achieve a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) criteria
- Duration of Response (DOR) [Up to approximately 3 years]
DOR is the time from initial tumor response of CR or PR to first documentation of progressive disease (PD) or death due to any cause, whichever occurs first
- Disease Control Rate (DCR) [Up to approximately 3 years]
DCR is the percentage of participants who achieve a CR, PR or stable disease
- Progression-Free Survival (PFS) [Up to approximately 3 years]
PFS is the time from start of study treatment to PD or death due to any cause, whichever occurs first
Eligibility Criteria
Criteria
Common Inclusion Criteria Required for ALL Patients
All patients must meet the common inclusion criteria required for all patients AND the respective criteria required for their specific disease for GBM and NSCLC (as applicable):
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Adults 18 years of age or older (at the time of providing informed consent)
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Patients with GBM or NSCLC who meet the disease-specific criteria and have disease progression after treatment with available therapies that are known to confer clinical benefit, or who refuse or are intolerant to treatment.
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Adequate bone marrow or organ function as demonstrated by all the following laboratory values:
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Estimated (using the Cockcroft-Gault equation) or measured creatinine clearance ≥ 60 mL/min.
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN. AST or ALT ≤5.0 × ULN in the presence of liver metastases.
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Total bilirubin <1.5 × ULN (for patients with Gilbert's syndrome, bilirubin <3.0 × ULN is allowed).
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Absolute neutrophil count (ANC) >1000 cells/μL
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Hemoglobin >8.5 g/dL. (Note: transfusion is allowed up to 1 week prior to enrollment)
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Platelet count >100,000/μL. (Note: transfusion is allowed up to 1 week prior to enrollment)
Inclusion Criteria Required for GBM Patients Only
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In addition to the common inclusion criteria above, patients with GBM must also meet the following inclusion criteria:
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Histologically confirmed diagnosis of GBM according to 2021 WHO criteria IDHwt (wild-type IDH) GBM and astrocytoma with molecular features of GBM).
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A radiological diagnosis of recurrent disease following available standard of care therapy of surgery, radiation, and/or TMZ. Disease may be evaluable or measurable for dose escalation cohorts but must be measurable by RANO criteria for enrollment on the disease specific expansion.
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Tumor evidence of EGFR alterations including amplification, variants, or mutations as determined in a local laboratory by NGS, RNAseq, FISH, IHC, or Array GCH
Inclusion Criteria Required for NSCLC Patients Only:
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Patients with NSCLC must meet all of the following inclusion criteria, in addition to the common inclusion criteria applicable for all patients:
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Histologically or cytologically confirmed NSCLC, without small cell lung cancer transformation.
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Locally advanced or metastatic disease, with or without CNS metastases. Disease may be evaluable or measurable for dose escalation cohorts but must be measurable by RECIST v1.1 criteria for enrollment on the disease specific expansion cohorts.
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Disease progression following or intolerance of standard of care:
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NSCLC with uncommon EGFR mutations (eg, G719X), following standard of care therapy with an EGFR inhibitor.
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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).
- EGFR mutations identified by NGS in the absence of other known resistance mutations (eg, T790M, MET)
Common Exclusion Criteria Required for ALL Patients:
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Known resistant mutations in tumor tissue or ctDNA, including EGFR T790M, EGFR exon 20 insertion mutations, MET (including MET amplification), KRAS, or HER2 (C805S, T798I, or T862A)
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GBM patient treated with a prior EGFR inhibitor
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Symptomatic Leptomeningeal disease. Asymptomatic untreated CNS and leptomeningeal disease is allowed and, when measurable, should be captured as target lesions
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Symptomatic brain metastases or spinal cord compression requiring increasing corticosteroids or urgent clinical intervention
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Unresolved Grade 2 or greater toxicity from prior therapy
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Significant cardiovascular disease
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Clinically significant abnormal electrocardiogram (ECG) findings
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1004 | Denver | Colorado | United States | 80218 |
| 2 | 1009 | Boston | Massachusetts | United States | 02115 |
| 3 | 1006 | Oklahoma City | Oklahoma | United States | 73104 |
| 4 | 1007 | Philadelphia | Pennsylvania | United States | 19107 |
| 5 | 1005 | Nashville | Tennessee | United States | 37203 |
| 6 | 1003 | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Black Diamond Therapeutics, Inc.
Investigators
- Study Director: Black Diamond Therapeutics, Black Diamond Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BDTX-1535-101