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

Phase 1

Active, not recruiting

• Conditions: Non-Small Cell Lung Cancer; Metastatic Lung Non-Small Cell Carcinoma; EGFR-TKI Resistant Mutation; Advanced Non-Small Cell Squamous Lung Cancer; Metastatic Lung Cancer; NSCLC; Advanced Lung Carcinoma; Epidermal Growth Factor Receptor C797S; Epidermal Growth Factor Receptor G719X; EGF-R Positive Non-Small Cell Lung Cancer
• Interventions: Drug: silevertinib (BDTX-1535) monotherapy; Drug: BDTX-1535 monotherapy

• Registration Number: NCT05256290
• Lead Sponsor: Black Diamond Therapeutics, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-15
• Study First Submitted QC: 2022-02-24
• Study First Posted: 2022-02-25
• Study Start: 2022-03-31
• Status Verified: 2025-03
• Primary Completion: 2025-07
• Last Update Submitted: 2025-07-09
• Last Update Posted: 2025-07-11
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Not provided

Exclusion Criteria

• 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.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)	silevertinib (BDTX-1535) monotherapy	* 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 Mutations	silevertinib (BDTX-1535) monotherapy	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)
Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation	silevertinib (BDTX-1535) monotherapy	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)
Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations	silevertinib (BDTX-1535) monotherapy	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.
Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)	BDTX-1535 monotherapy	* 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 Mutations	BDTX-1535 monotherapy	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)
Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation	BDTX-1535 monotherapy	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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)	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)	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)	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	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	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)	At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2

Trial Locations

Locations (41)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

City of Hope Comprehensive Cancer Center (Duarte Campus); 🇺🇸 Duarte, California, United States

City of Hope Huntington Beach; 🇺🇸 Huntington Beach, California, United States

City of Hope Orange County Lennar Foundation Cancer Center; 🇺🇸 Irvine, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Valkyrie Clinical Trials; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Cancer Center; 🇺🇸 Lone Tree, Colorado, United States

Sibley Memorial Hospital Johns Hopkins Medicine; 🇺🇸 Washington, District of Columbia, United States

Mayo Clinic- Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Scroll for more (31 remaining)