Non-Small Cell Lung CancerPhase 1/2NCT05256290

Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations

A Phase 1/2 study testing silevertinib (BDTX-1535) monotherapy in people with Non-Small Cell Lung Cancer and Advanced Non-Small Cell Squamous Lung Cancer, run by Black Diamond Therapeutics, Inc. at 25 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-Small Cell Lung Cancer, Advanced Non-Small Cell Squamous Lung Cancer, Metastatic Lung Non-Small Cell Carcinoma
What is being tested?: silevertinib (BDTX-1535) monotherapy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 25 sitesUnited States
Study dates: 31 Mar 2022to Dec 2027
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC.
Any history of interstitial lung disease related to EGFR TKI use.
Symptomatic or radiographic leptomeningeal disease.
Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.
Unresolved toxicity from prior therapy.

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Significant cardiovascular disease.
Major surgery within 4 weeks of study entry or planned during study.
Ongoing or recent anticancer therapy or radiation therapy.
Evidence of malignancy (other than study-specific malignancies) requiring active therapy within the next 2 years.
Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV) carrier.
Poorly controlled gastrointestinal disorders.

Trial locations and contacts

25 sites in 1 country.

City, postcode or hospital

25 sites in 1 country

United States25 sites

Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
University of Alabama
Birmingham, Alabama, 35294
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
UNC Hospitals - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27514
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Next Ocology
Fairfax, Virginia, 22031
University of Kansas Cancer Center
Fairway, Kansas, 66205
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
UHP- University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
City of Hope Huntington Beach
Huntington Beach, California, 92648
City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, 92618
Mayo Clinic- Jacksonville
Jacksonville, Florida, 32224
Cedars Sinai Medical Center
Los Angeles, California, 90048
Miami Cancer Institute - Baptist Health South Florida
Miami, Florida, 33176
Tennessee Oncology
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Columbia University Irving Medical Center
New York, New York, 10032
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Mayo Clinic- Rochester
Rochester, Minnesota, 55905
Fred Hutchinson Cancer Center/University of Washington
Seattle, Washington, 98109
Siteman Cancer Center
St Louis, Missouri, 63110
Montefiore Medical Center
The Bronx, New York, 10461
Sibley Memorial Hospital Johns Hopkins Medicine
Washington D.C., District of Columbia, 20016

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About this study

Official title: A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer

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 silevertinib (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 silevertinib (BDTX-1535) monotherapy by mouth in 21-day cycles.

Phase 1 enrollment is now complete. Phase 2 is currently ongoing.

Conditions: Non-Small Cell Lung Cancer, Advanced Non-Small Cell Squamous Lung Cancer, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Cancer, NSCLC, Advanced Lung Carcinoma
Being tested: silevertinib (BDTX-1535) monotherapy
Keywords: EGFR alterations, EGFR L858R, EGFR Exon 19 del, EGFR inhibitor, intrinsic resistance NSCLC EGFR, acquired resistance NSCLC EGFR, intracranial disease, brain metastases, central nervous system metastases, CNS metastases, uncommon NSCLC EGFR mutations, C797S acquired resistance EGFR mutation, non-classical NSCLC EGFR mutations, classical NSCLC EGFR mutations, EGFR PACC NSCLC mutations, EGFR E709A/G/K/Q/V, EGFR E709_T710delinsD/T, EGFR G719A/C/D/R/S, EGFR G724S, EGFR L718Q/V
Medical subject headings: Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

silevertinib (BDTX-1535) monotherapyDrug
Silevertinib (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.

Study groups in NCT05256290
Study group	Role	What they receive
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) Receives: Drug: silevertinib (BDTX-1535) monotherapy
Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations	Experimental	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) Receives: Drug: silevertinib (BDTX-1535) monotherapy
Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation	Experimental	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) Receives: Drug: silevertinib (BDTX-1535) monotherapy
Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations	Experimental	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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Dose-limiting toxicities (DLTs) in Cycle 1
Measured: The first treatment 21-day cycle (Cycle 1)
Phase 2: To assess antitumor efficacy of silevertinib (BDTX-1535)
Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1
Measured: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)

Secondary outcomes (8)

Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)
Measured: 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
Measured: 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)
Phase 1: To assess the preliminary antitumor activity of silevertinib (BDTX-1535) by objective response as assessed by RECIST version 1.1 (for patients with NSCLC) or Response Assessment in Neuro-oncology (RANO) (for patients with GBM)
Measured: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Phase 1: To assess the effect of tablet formulation on the plasma concentration of silevertinib (BDTX-1535)
Measured: Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days)
Phase 1: To assess the effect of food on the plasma concentration of silevertinib (BDTX-1535)
Measured: Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days)
Phase 2: To assess duration of tumor response by RECIST version 1.1
Measured: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Phase 2: To assess progression free survival by RECIST version 1.1
Measured: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Phase 2: To determine the optimal dosage of silevertinib (BDTX-1535) (100 mg or 200 mg daily dose)
Measured: At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Mar 2022Dec 2027

First posted25 Feb 2022
Study start31 Mar 2022
Primary completion3 Nov 2025
Study completionDec 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 200 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05256290
Sponsor's protocol ID: BDTX-1535-101
Status last verified: Jul 2026
First submitted: 15 Feb 2022
Last updated: 22 Jul 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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