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

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

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

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

Pharmacokinetics, Pharmacodynamics and Clinical data update from phase 0/1 trial for BDTX-1535 in recurrent glioblastoma patients with EGFR alterations. (EANO 2025) - "For recurrent GBM patients, BDTX-1535 achieves pharmacologically relevant concentrations in Gd-nonenhancing tumor tissue and is associated with suppression of EGFR phosphorylation. Expected safety signals were observed but manageable. Based on these encouraging findings, the trial is being expanded to enroll newly-diagnosed EGFR-positive GBM patients."

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

Black Diamond Therapeutics Reports Second Quarter 2025 Financial Results and Provides Corporate Update (Black Diamond Therapeutics Press Release) - "In July 2025, Black Diamond completed enrollment (n=43) in the Phase 2 trial of silevertinib in frontline non-small cell lung cancer (NSCLC) patients with non-classical EGFR mutations. In the fourth quarter of 2025, Black Diamond expects to disclose objective response rate (ORR) and preliminary duration of response (DOR) data from all patients (n=43) in the Phase 2 trial of silevertinib in frontline NSCLC with non-classical EGFR mutations. Black Diamond is exploring partnership opportunities in NSCLC and glioblastoma (GBM) to advance silevertinib into pivotal development. The Company plans to solicit U.S. Food and Drug Administration (FDA) feedback on a potential registrational path in frontline EGFRm NSCLC in 1H 2026, when progression free survival (PFS) data from the ongoing Phase 2 trial becomes available."

Enrollment closed • FDA event • P1/2 data • Glioblastoma • Non Small Cell Lung Cancer

Overcoming triple mutant EGFR-tyrosine kinase barriers in the therapeutics of non-small cell lung cancer: a patent review on fourth-generation inhibitors (2017-2024). (PubMed, Expert Opin Ther Pat) - "This review highlights the significance of fourth-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) in addressing acquired resistance mechanisms, such as the C797S mutation, which compromises the efficacy of third-generation inhibitors like Osimertinib and explores their potential to revolutionize NSCLC treatment through enhanced molecular specificity. Preclinical trials highlight the potential of sulfonyl and phosphine oxide-based compounds for their potency, selectivity, and favorable pharmacokinetics. Promising clinical trials with inhibitors like BDTX-1535, JIN-A02, and HS-10504 could redefine NSCLC treatment, with future success likely relying on innovative strategies, such as combination therapies, to combat resistance and enhance efficacy."

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. | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma

Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions (clinicaltrials.gov) - P1 | N=82 | Recruiting | Sponsor: St. Joseph's Hospital and Medical Center, Phoenix | N=34 ➔ 82 | Trial completion date: Oct 2025 ➔ Sep 2027 | Trial primary completion date: May 2025 ➔ Sep 2026

Enrollment change • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor • EGFR

Black Diamond Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "...Upcoming Milestones: BDTX-1535: In the fourth quarter of 2025, Black Diamond expects to disclose initial Phase 2 clinical data for BDTX-1535 in newly diagnosed patients with non-classical epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) (NCT05256290) and plans to solicit U.S. Food and Drug Administration (FDA) feedback on a potential pivotal registrational path."

FDA event • P2 data • Non Small Cell Lung Cancer

A clinical review on third and fourth generation EGFR tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. (PubMed, Bioorg Med Chem) - "This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors."

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

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 • Malignant 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

Black Diamond Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Black Diamond anticipates the following upcoming key milestones for BDTX-1535: (i) Initial Phase 2 clinical data in newly diagnosed patients with non-classical epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) in the second quarter of 2025; (ii) Updated Phase 2 clinical data in patients with recurrent EGFRm NSCLC with a broad spectrum of classical, non-classical, and C797S resistance mutations in the second half of 2025; (iii) Planning to solicit U.S. Food and Drug Administration (FDA) feedback on a potential pivotal registrational path for BDTX-1535 in newly diagnosed EGFRm NSCLC patients in the second half of 2025; (iv) Expansion of the investigator sponsored 'window of opportunity' trial (also known as a Phase 0/1 'Trigger' trial) into a Phase 0/2 trial in newly diagnosed glioblastoma (GBM) patients with epidermal growth factor receptor (EGFR) aberrations in the first quarter of 2025."

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

Targeting C797S mutations and beyond in non-small cell lung cancer-a mini-review. (PubMed, Transl Cancer Res) - "BDTX-1535 is an orally bioavailable, brain-penetrating, mutation-selective, irreversible EGFR inhibitor with significant antitumour activity in NSCLCs and glioblastomas (phase I/II trials ongoing). It should be noted that in up to 50% of all NSCLC patients who progress following osimertinib or other EGFR TKI therapy no underlying resistance mechanism can be identified suggesting that non-mutational signal transduction pathways may also be operative, and intratumoural heterogeneity has been found to be a major contributor to resistance and it consists of three main mechanisms: (I) drug-tolerant persister (DTP) cells, (II) chromosomal instability, and (III) extrachromosomal extracellular DNA (ecDNA) (seen in over 50% of NSCLCs) suggesting that novel EGFR TKIs will include many challenges in sufficiently targeting on-target resistance mechanisms. The development of novel drugs that can overcome TKI resistance in NSCLC patients harbouring the C797S mutation and beyond is,..."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase 0/1 study of BDTX-1535 in recurrent glioblastoma (GBM) patients with EGFR alterations or fusions. (SNO 2024) - "BDTX-1535 is well-tolerated in recurrent HGG patients, achieves pharmacologically relevant concentrations in non-enhancing tumor tissue, and is associated with suppression of EGFR signaling. Efficacy data accompanying this PK/PD response will be reported."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Malignant Glioma • Oncology • Solid Tumor • EGFR