silevertinib (BDTX-1535) / Black Diamond Therap - LARVOL DELTA

Safety and efficacy results of the phase 2 study of silevertinib (BDTX-1535) in treatment-naïve patients with non-small cell lung cancer with non-classical EGFR mutations. (ASCO 2026) - P1/2 | "Funded by Black Diamond Therapeutics Clinical Trial Registration Number: NCT05256290 Background: Non-classical mutations (NCM) of epidermal growth factor receptor (EGFR) represent a broad group of oncogenic mutations in non-small cell lung cancer (NSCLC), often associated with resistance to osimertinib (e.g., P-loop and αC-helix compressing [PACC] mutations). Silevertinib demonstrated robust antitumor activity in treatment-naïve pts with a broad spectrum of NCM EGFR driver mutations with high intracranial activity in pts with brain metastases. The safety profile was consistent with the known AEs of the EGFR TKI class. *No pts with classical (E746_A750del or L858R) mutations were enrolled."

Clinical • P2 data • CNS Disorders • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

Randomized phase 2 study to evaluate the efficacy and safety of silevertinib in combination with temozolomide in newly diagnosed patients with EGFRvIII-positive IDHwt MGMT unmethylated glioblastoma (SNO 2026) - No abstract available

Clinical • Combination therapy • P2 data • Brain Cancer • Glioblastoma • Solid Tumor • MGMT

Safety and efficacy results of the phase 2 study of silevertinib (BDTX-1535) in previously treated patients with non-small cell lung cancer with non-classical and C797S EGFR mutations. (ASCO 2026) - P1/2 | " Patients (pts) with recurrent NSCLC following ≤ 2 lines of therapy with only 1 prior EGFR TKI (osimertinib preferred) and tumors positive for NCM (NCM Cohort) or C797S mutation (C797S Cohort) were enrolled based on a local molecular test. Silevertinib demonstrated antitumor activity at 200 mg orally once daily in patients with recurrent NSCLC, EGFR NCMs, and acquired resistance C797S mutation with a safety profile consistent with the EGFR TKI class."

Clinical • P2 data • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

Recent advances in synthetic strategies of fourth-generation EGFR tyrosine kinase inhibitors under clinical trials for the treatment of resistant non-small cell lung cancer (NSCLC). (PubMed, Bioorg Chem) - "The present review summarizes recent advances in the synthetic strategies and biological profiles of fourth-generation EGFR-TK inhibitors currently undergoing clinical investigation for resistant Non-Small Cell Lung Cancer (NSCLC) to overcome the C797S mutation associated with Osimertinib. Representative clinical candidates, including TQB-3804, BPI-361175, BLU-945, BBT-176, BDTX-1535, QLH11811, HS-10375, and H002, are discussed with particular emphasis on synthetic route design, key intermediates, medicinal chemistry optimization, and pharmacological activity...In addition, advances in scaffold design, phosphine oxide incorporation, and conformationally optimized heterocyclic frameworks have contributed significantly to the development of next-generation mutant-selective inhibitors. Overall, this review provides a contemporary overview of synthetic innovations in fourth-generation EGFR inhibitor development and highlights emerging strategies for overcoming..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

BDTX-1535-101: Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Black Diamond Therapeutics, Inc. | Trial completion date: Jun 2026 ➔ Dec 2027

Trial completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Randomized phase 2 study to evaluate the efficacy and safety of silevertinib in combination with temozolomide in newly diagnosed patients with EGFRvIII-positive IDHwt MGMT unmethylated glioblastoma. (ASCO 2026) - P1, P1/2 | "The primary endpoint for Part 2 is progression free survival by blinded independent central review using Response Assessment in Neuro-Oncology (RANO2.0) criteria. Key inclusion criteria."

Clinical • Combination therapy • P2 data • Brain Cancer • Glioblastoma • Solid Tumor • MGMT

Black Diamond Therapeutics Announces Positive Phase 2 Results for Silevertinib in Frontline NSCLC Patients with EGFR Non-Classical Mutations (GlobeNewswire) - "These data will be presented...at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on Saturday, May 30, 2026....43 patients with 1L NSCLC were enrolled at a 200 mg once daily dose of silevertinib....Preliminary median Progression-free Survival (mPFS) is 15.2 months (95% CI: 10.8; NE). Median duration of response (DOR) had not been reached (95%CI: 7.0, NE). 23 of 43 patients (53%) remain on therapy, with longest at 23.5 months....No patients developed de novo brain metastases. Previously disclosed CNS Objective Response Rate (ORR by RANO-BM) remained at 86%."

P2 data • Non Small Cell Lung Cancer

Black Diamond Therapeutics…will host a webcast for investors to present updated results from its ongoing Phase 2 trial of silevertinib in frontline patients with EGFR mutated non-small cell lung cancer on Thursday, May 21, 2026, at 5:30 p.m. ET. (GlobeNewswire)

P2 data • Non Small Cell Lung Cancer

Characterization of fourth-generation EGFR inhibitors in binding experiments with C797S mutant EGFR and cell-based assays with osimertinib-resistant non-small cell lung cancer cell lines (AACR 2024) - "Fourth-generation EGFR inhibitors and combinations with other targeted agents are potential strategies to overcome osimertinib resistance or to increase its efficacy.Three fourth-generation EGFR inhibitors were profiled in biochemical and cell-based assays: BDTX-1535, BLU-945, and JBJ-09-063. Profiling results of the three fourth-generation EGFR inhibitors in the osimertinib-resistant cell lines and on a panel of more than one hundred human cancer cell lines will be presented.Reference: [1] Bertran-Alamillo et al. Nature Communications 10, 1812; 2019"

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

IL-1 alpha expression induces drug resistance to all generations of EGFR inhibitors in HNSCC (AACR 2026) - "The goal of this study is to determine if IL-1α-induced drug resistance is maintained across second, third and fourth generation EGFR TKIs.EGFR wildtype-positive HNSCC cells (FaDu, Cal-27 and SQ20B) were treated with the IC50 doses of erlotinib (first generation), afatinib (second generation), osimertinib (third generation), and silevertinib (fourth generation) EGFR TKIs for 48 h. Cell viability responses to EGFR TKIs were assessed using MTT assays...Manipulation of IL-1 expression and signaling was performed using neutralizing antibodies to human IL-1α antibody (nIL-1α) and IL-1β (nIL-1β), and the human IL-1 receptor antagonist - anakinra...Collectively, these findings identify IL-1α expression as a central mediator of poor response and resistance to all EGFR TKIs via an EGFR mutation-independent mechanism. Hence, targeting IL-1α expression/signaling could be a promising strategy to improve long term tumor response to EGFR TKIs in HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL1A • IL1B • IL6

Assessment of neuro-pharmacokinetic behavior of BDTX-1535 in brain tumor patients by a validated LC-MS/MS method (AACR 2025) - P1 | "The validated method is currently employed to assess BDTX-1535 levels in human brain tumor tissue, CSF, blood and plasma in an ongoing trial on recurrent high-grade glioma patients (NCT06072586). Initial results of measured total and unbound drug levels in the gadolinium-enhancing and non-enhancing brain tumor regions indicate significant brain penetration ability of BDTX-1535 in high-grade glioma patients."

Clinical • PK/PD data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • EGFR

A phase 0/1 'trigger' trial of BDTX-1535 in recurrent glioblastoma (GBM) patients with EGFR alterations or fusions (AACR 2025) - "For recurrent GBM patients, BDTX-1535 achieves pharmacologically relevant concentrations in Gd-nonenhancing tumor tissue and is associated with suppression of EGFR phosphorylation. Study expansion into MGMT-unmethylated, newly-diagnosed GBM patients is planned."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR • MGMT

BDTX-1535: A MasterKey EGFR inhibitor targeting classical and non-classical oncogenic driver mutations and the C797S acquired resistance mutation to address the evolving molecular landscape of EGFR mutant NSCLC (AACR 2024) - "We further present the profile for BDTX-1535 as a MasterKey EGFR inhibitor designed to address this evolved EGFR mutational landscape and tested against over >50 EGFR mutations. We also show how BDTX-1535 can address classical EGFR mutations in addition to on target mechanisms of resistance post osimertinib with potency against C797S as well as non-classical mutations affecting both the intracellular and extracellular domains, including L718X, E709X, S784F, V834L and A289V."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII (clinicaltrials.gov) - P2 | N=162 | Recruiting | Sponsor: Black Diamond Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR

Black Diamond anticipates the following upcoming key milestones for silevertinib (GlobeNewswire) - "(i) Presentation of updated clinical data from our Phase 2 trial in patients with non-classical EGFR NSCLC in both the recurrent setting and the frontline setting, including preliminary duration of response (DOR) and progression-free survival (PFS) data for frontline EGFRm patients, at a medical meeting in the second quarter of 2026 (NCT05256290); (ii) Initiation of a randomized Phase 2 trial in patients with newly diagnosed EGFR-altered GBM in the second quarter of 2026 (NCT07326566)."

P2 data • Trial status • Glioblastoma • Non Small Cell Lung Cancer

Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII (clinicaltrials.gov) - P2 | N=162 | Not yet recruiting | Sponsor: Black Diamond Therapeutics, Inc.

New P2 trial • Brain Cancer • CNS Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR

BDTX-1535-101: Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Black Diamond Therapeutics, Inc. | Trial primary completion date: Jul 2025 ➔ Nov 2025

Trial primary completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma

Silevertinib Phase 2 1L NSCLC Initial Clinical Results and Program Update (GlobeNewswire) - "For the 43 patients enrolled, preliminary efficacy data is as follows: 25 confirmed partial responses, 1 confirmed complete response; 60% Objective Response Rate (ORR by RECIST 1.1); 86% CNS ORR (by RANO-BM); 91% disease control rate (DCR). Initial duration of treatment data: 29 patients remain on therapy (5/29 after progression), longest ongoing for >19 months....The Company expects to present updated results from the Phase 2 NSCLC trial, including Duration of Response (DOR) and Progression-free Survival (PFS) data in both the recurrent (83 patients) and frontline (43 patients) settings, at a medical meeting in the second quarter of 2026."

P2 data • Non Small Cell Lung Cancer

Black Diamond Therapeutics Announces…Plans for a Phase 2 Trial of Silevertinib in GBM (GlobeNewswire) - "Black Diamond plans to initiate a randomized Phase 2 trial in newly diagnosed GBM patients in the first half of 2026, with preliminary data expected in 2028."

New P2 trial • P2 data • Glioblastoma

Integrated pharmacokinetics, pharmacodynamics, and clinical data update from phase 0/1 trial for BDTX-1535 in newly-diagnosed and recurrent glioblastoma patients with EGFR alterations. (SNO 2025) - "BDTX-1535 reaches therapeutic levels in infiltrative GBM tissue, with associated biomarker suppression. Safety signals were expected and manageable. Arm C enrollment is ongoing."

Clinical data • PK/PD data • Brain Cancer • Glioblastoma • Solid Tumor • EGFR • MGMT

Integrated pharmacokinetics, pharmacodynamics, and clinical data update from phase 0/1 trial for BDTX-1535 in newly-diagnosed and recurrent glioblastoma patients with EGFR alterations. (SNO 2025) - "BDTX-1535 reaches therapeutic levels in infiltrative GBM tissue, with associated biomarker suppression. Safety signals were expected and manageable. Arm C enrollment is ongoing."

Clinical data • PK/PD data • Brain Cancer • Glioblastoma • Solid Tumor • EGFR • MGMT

A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (rHGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions (clinicaltrials.gov) - P1 | N=82 | Recruiting | Sponsor: St. Joseph's Hospital and Medical Center, Phoenix | Trial completion date: Sep 2027 ➔ Dec 2027 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • EGFR

Integrated pharmacokinetics, pharmacodynamics, and clinical data update from phase 0/1 trial for BDTX-1535 in newly-diagnosed and recurrent glioblastoma patients with EGFR alterations. (WFNOS 2025) - "BDTX-1535 reaches therapeutic levels in infiltrative GBM tissue, with associated biomarker suppression. Safety signals were expected and manageable. Arm C enrollment is ongoing."

Clinical data • PK/PD data • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • EGFR • MGMT

Integrated pharmacokinetics, pharmacodynamics, and clinical data update from phase 0/1 trial for BDTX-1535 in newly-diagnosed and recurrent glioblastoma patients with EGFR alterations. (WFNOS 2025) - "BDTX-1535 reaches therapeutic levels in infiltrative GBM tissue, with associated biomarker suppression. Safety signals were expected and manageable. Arm C enrollment is ongoing."

Clinical data • PK/PD data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR • MGMT

Black Diamond Therapeutics…Provides Corporate Update (The Manila Times) - "ORR and preliminary duration of treatment data for the Phase 2 trial of silevertinib in 1L patients with non-classical EGFRm NSCLC on track for this quarter....The Company intends to solicit U.S. Food and Drug Administration (FDA) feedback on a potential registrational path in frontline EGFR mutant NSCLC in the first half of 2026, when progression free survival (PFS) data from the ongoing Phase 2 trial becomes available."

FDA event • P2 data • Non Small Cell Lung Cancer