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Silevertinib

Phase 2

Glioblastoma (GBM) | Small molecule | Oncology |Black Diamond Therapeutics, Inc.|Last Updated: Sep 3, 2026

Target and mechanism

Molecular targetEGFR
Target class-Tinib (Kinase)
ModalitySmall molecule

Also known as silevertinib (BDTX-1535) monotherapy, silevertinib monotherapy

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment162

FDA Designations

No designations recorded

Clinical trial landscape

Silevertinib · 2 trials · 17 indications

Phase 2 1Phase 1 1
NCT07326566Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIIIGlioblastoma (GBM)
RECRUITING162 Analytics
PHASE2RECRUITING
Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII
Glioblastoma (GBM)Unlock trial analytics

Study Endpoints

Primary Endpoints

Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
12 months

Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.

Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of silevertinib (BDTX-1535)
The first treatment 21-day cycle (Cycle 1)

Dose-limiting toxicities (DLTs) in Cycle 1

Phase 2: To assess antitumor efficacy of silevertinib (BDTX-1535)
Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)

Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1

Secondary Endpoints

Overall Survival
18 months
Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)
Through study completion, approximately 1 year
Phase 1 and Phase 2: To characterize the plasma concentration of silevertinib (BDTX-1535) following single and multiple dosing
Cycle 1 Days 1, 2, 15, and 16, Cycles 2 to 5 Day 1, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 21 days)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
silevertinib and temozolomideEXPERIMENTALsilevertinib at dose determined in Part 1 until disease progression in combination with temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
temozolomideACTIVE_COMPARATORtemozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)EXPERIMENTAL* 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)
Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver MutationsEXPERIMENTALAdvanced/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)
Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) MutationEXPERIMENTALAdvanced/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)
Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver MutationsEXPERIMENTALTreatment-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.

Interventions

NameTypeDescription
silevertinib in combination with temozolomideDRUGParticipants enrolled into Part 1 (Safety Lead-In) or randomized to Arm A in Part 2 will receive silevertinib at dose determined in Part 1 until disease progression in combination with temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles.
temozolomide (TMZ)DRUGParticipants randomized to Arm B will receive temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
silevertinib (BDTX-1535) monotherapyDRUGSilevertinib (BDTX-1535) is a 4th generation irreversible brain penetrant EGFR MasterKey inhibitor, which targets a family of oncogenic EGFR classical and non-classical driver and resistance mutations in NSCLC.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites29

Key Inclusion Criteria: * Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT). * Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification). * For Part ...

Countries:United States
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Recent Changes (Last 90 Days)

LOWSep 3, 2026NCT07326566lastUpdatePostDate: changed
LOWSep 3, 2026NCT07326566lastUpdatePostDate: changed
LOWAug 28, 2026NCT07326566lastUpdatePostDate: changed
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LOWAug 21, 2026NCT07326566lastUpdatePostDate: changed
LOWAug 21, 2026NCT07326566lastUpdatePostDate: changed
LOWAug 14, 2026NCT07326566lastUpdatePostDate: changed
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LOWJul 24, 2026NCT07326566lastUpdatePostDate: changed
LOWJul 24, 2026NCT07326566lastUpdatePostDate: changed
MEDIUMJul 22, 2026NCT05256290Completion: 2026-06 → 2027-12
MEDIUMJul 22, 2026NCT05256290Completion: 2026-06 → 2027-12
LOWJul 17, 2026NCT07326566lastUpdatePostDate: changed
LOWJul 17, 2026NCT07326566lastUpdatePostDate: changed
LOWJul 17, 2026NCT07326566lastUpdatePostDate: changed

Frequently asked questions about Silevertinib

What is silevertinib monotherapy used for?

Silevertinib monotherapy is an investigational small molecule being studied for Non-Small Cell Lung Cancer (NSCLC), including advanced and metastatic forms. It is also being evaluated in glioblastoma. The drug is designed for patients with specific EGFR mutations, such as the C797S and G719X mutations, and for those resistant to EGFR-TKI therapy.

What does silevertinib target?

Silevertinib targets EGFR, the epidermal growth factor receptor, a kinase involved in cell growth. As a -tinib class kinase inhibitor, it is being developed to address EGFR mutations like C797S and G719X in Non-Small Cell Lung Cancer. The drug aims to inhibit mutant EGFR signaling in tumors that have developed resistance to earlier EGFR-targeted therapies.

Who is developing silevertinib?

Silevertinib is being developed by Black Diamond Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker BDTX. The company is conducting clinical research on this investigational drug for Non-Small Cell Lung Cancer and glioblastoma.

What phase is silevertinib in?

Silevertinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The ongoing Phase 1/2 study is currently active but not recruiting participants, and it is evaluating the drug in patients with glioblastoma or Non-Small Cell Lung Cancer with EGFR mutations.

What clinical trials is silevertinib in?

Silevertinib is being studied in a single clinical trial registered as NCT05256290. This Phase 1/2 study enrolls patients with glioblastoma or Non-Small Cell Lung Cancer with EGFR mutations, including advanced squamous lung cancer and metastatic disease. The trial is active in the United States and targets approximately 200 participants aged 18 and older.

Is silevertinib the same as BDTX-1535?

Yes, silevertinib is also known as BDTX-1535. The drug is referred to as silevertinib (BDTX-1535) in clinical research. It is being studied as a monotherapy and in combination with temozolomide, though the current trial focuses on monotherapy for EGFR-mutant cancers.