Black Diamond Therapeutics Announces Initial Phase 2 Data Demonstrating Robust Anti-tumor Activity of BDTX-1535 in Patients with Recurrent EGFRm NSCLC who Present with a Broad Spectrum of Classical, Non-classical, and C797S Resistance Mutations
Black Diamond Therapeutics has reported promising initial Phase 2 data for BDTX-1535 in patients with recurrent EGFRm NSCLC. Key findings include:
- A 200 mg daily dose selected for pivotal development, showing a favorable tolerability profile
- Preliminary ORR of 42% in 19 patients at 200 mg with on-target resistance EGFR mutations
- Encouraging durability with DOR of approximately 8 months or more for the first 3 patients with a PR
- 14 of 19 patients remain on treatment
The company anticipates regulatory feedback on the registration path in Q1 2025 and expects initial results of BDTX-1535 in first-line NSCLC patients with non-classical EGFR mutations in the same quarter.
Black Diamond Therapeutics ha riportato dati iniziali promettenti della Fase 2 per BDTX-1535 in pazienti con NSCLC ricorrente con mutazioni EGFR. I risultati principali includono:
- Una dosi giornaliera di 200 mg selezionata per lo sviluppo cruciale, mostrando un profilo di tollerabilità favorevole
- ORR preliminare del 42% in 19 pazienti a 200 mg con mutazioni EGFR di resistenza diretta
- Durabilità incoraggiante con un DOR di circa 8 mesi o più per i primi 3 pazienti con una PR
- 14 dei 19 pazienti rimangono in trattamento
L'azienda prevede un riscontro normativo sul percorso di registrazione nel primo trimestre del 2025 e si aspetta risultati iniziali di BDTX-1535 nei pazienti con NSCLC di prima linea con mutazioni EGFR non classiche nello stesso trimestre.
Black Diamond Therapeutics ha reportado datos iniciales prometedores de la Fase 2 para BDTX-1535 en pacientes con NSCLC recurrente con mutaciones EGFR. Los hallazgos clave incluyen:
- Una dosis diaria de 200 mg seleccionada para el desarrollo crucial, mostrando un perfil de tolerabilidad favorable
- ORR preliminar del 42% en 19 pacientes a 200 mg con mutaciones EGFR de resistencia dirigida
- Durabilidad alentadora con un DOR de aproximadamente 8 meses o más para los primeros 3 pacientes con una PR
- 14 de 19 pacientes continúan en tratamiento
La empresa anticipa recibir comentarios regulatorios sobre la ruta de registro en el primer trimestre de 2025 y espera resultados iniciales de BDTX-1535 en pacientes de NSCLC de primera línea con mutaciones EGFR no clásicas en el mismo trimestre.
Black Diamond Therapeutics는 EGFR 돌연변이가 있는 재발성 NSCLC 환자에 대한 BDTX-1535의 2상 초기 데이터가 유망하다고 보고했습니다. 주요 발견 사항은 다음과 같습니다:
- 중요한 개발을 위해 선택된 200mg의 일일 복용량, 유리한 내약성 프로필을 보여줍니다
- 목표 내성 EGFR 변이가 있는 200mg의 19명 환자에서 42%의 ORR이 preliminar합니다
- PR이 있는 첫 3명 환자에 대해 약 8개월 이상의 DOR로 격려되는 내구성
- 19명 중 14명이 치료를 계속하고 있습니다
회사는 2025년 1분기에 등록 경로에 대한 규제 피드백을 예상하고 있으며, 같은 분기에 비전형성 EGFR 돌연변이가 있는 1차 NSCLC 환자에 대한 BDTX-1535의 초기 결과를 기대하고 있습니다.
Black Diamond Therapeutics a rapporté des données préliminaires prometteuses de la phase 2 pour le BDTX-1535 chez des patients atteints de NSCLC EGFRm récidivant. Les principaux résultats incluent :
- Une posologie quotidienne de 200 mg sélectionnée pour le développement pivot, affichant un profil de tolérance favorable
- Taux de réponse global préliminaire de 42% chez 19 patients à 200 mg présentant des mutations EGFR de résistance ciblée
- Durabilité encourageante avec un DOR d'environ 8 mois ou plus pour les 3 premiers patients ayant atteint une PR
- 14 des 19 patients restent sous traitement
L'entreprise s'attend à des retours réglementaires sur la voie d'enregistrement au premier trimestre 2025 et prévoit des résultats initiaux de BDTX-1535 chez des patients NSCLC en première ligne présentant des mutations EGFR non classiques au cours du même trimestre.
Black Diamond Therapeutics hat vielversprechende erste Phase-2-Daten für BDTX-1535 bei Patienten mit wiederkehrendem EGFRm NSCLC berichtet. Zu den wichtigsten Ergebnissen gehören:
- Eine tägliche Dosis von 200 mg, die für die entscheidende Entwicklung ausgewählt wurde und ein günstiges Verträglichkeitsprofil zeigt
- Eine vorläufige ORR von 42% bei 19 Patienten mit 200 mg und zielgerichteten EGFR-Mutationen
- Ermutigende Beständigkeit mit einem DOR von etwa 8 Monaten oder mehr für die ersten 3 Patienten mit PR
- 14 von 19 Patienten bleiben in Behandlung
Das Unternehmen erwartet im ersten Quartal 2025 regulatorisches Feedback zum Zulassungsweg und rechnet im gleichen Quartal mit ersten Ergebnissen von BDTX-1535 bei NSCLC-Patienten erster Linie mit nicht klassischen EGFR-Mutationen.
- Preliminary ORR of 42% in patients with on-target resistance EGFR mutations
- Encouraging durability with DOR of approximately 8 months or more for first 3 patients with PR
- 14 of 19 patients remain on treatment, indicating potential long-term efficacy
- Favorable tolerability profile at 200 mg dose
- Potential for BDTX-1535 to address unmet medical need in recurrent EGFRm NSCLC
- Only 5 out of 19 patients achieved confirmed partial response
- data on long-term efficacy and safety beyond 8 months
- Regulatory feedback on registration path not expected until Q1 2025
- 70% of patients experienced rash as a treatment-related adverse event
Insights
The Phase 2 data for BDTX-1535 in EGFRm NSCLC patients is highly encouraging. The 42% ORR in patients with on-target resistance mutations is impressive, especially considering the options for these patients after osimertinib failure. The durability of response, with some patients showing 8+ months DOR, is particularly noteworthy in this difficult-to-treat population.
The favorable safety profile at the 200 mg dose is crucial, as it allows for continuous treatment. The lack of grade 3/4 diarrhea and severe rash cases suggest good tolerability, which is essential for quality of life and treatment adherence in cancer patients.
The potential expansion into first-line treatment for non-classical EGFR mutations could significantly broaden BDTX-1535's market. However, we need to see the Q1 2025 data to assess its competitiveness against existing first-line options.
This Phase 2 data represents a significant milestone for Black Diamond Therapeutics. The positive efficacy and safety results could potentially position BDTX-1535 as a new standard of care in the recurrent EGFRm NSCLC setting, a market with high unmet need and substantial commercial potential.
Investors should note the upcoming catalysts:
- Regulatory feedback on registration path in Q1 2025
- Initial results in first-line NSCLC patients with non-classical EGFR mutations in Q1 2025
These events could significantly impact BDTX's
As an oncologist, I find the BDTX-1535 data quite promising. The 42% ORR in heavily pretreated patients with on-target resistance mutations is clinically meaningful. Most importantly, the durability of response, with some patients showing 8+ months DOR, could translate to significant survival benefits.
The safety profile is manageable, with mostly grade 1-2 rash and diarrhea. This is important for maintaining dose intensity and quality of life. The potential for BDTX-1535 in the first-line setting for non-classical EGFR mutations is intriguing, as these patients currently lack targeted options.
However, we need more mature data on progression-free survival and overall survival to fully assess BDTX-1535's impact. The upcoming first-line data in Q1 2025 will be critical in determining its potential to change the treatment paradigm in EGFRm NSCLC.
BDTX-1535 dose of 200 mg daily selected for pivotal development; favorable tolerability profile and no new safety signals observed
Preliminary ORR of
Encouraging durability with DOR of approximately 8 months or more for first 3 patients with a PR; 14 of 19 patients remain on treatment
Regulatory feedback on registration path anticipated in Q1 2025
Initial results of BDTX-1535 in first-line NSCLC patients with non-classical EGFR mutations expected Q1 2025
CAMBRIDGE, Mass., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, today reported initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor (EGFR)-mutant (EGFRm) non-small cell lung cancer (NSCLC).
“Patients often become resistant to osimertinib with the emergence of on-target resistance EGFR mutations,” said Sergey Yurasov, M.D., Chief Medical Officer of Black Diamond Therapeutics. “Our preliminary Phase 2 data demonstrate the potential of BDTX-1535 to deliver durable responses for these patients.”
“Patients with recurrent EGFRm NSCLC have few treatment options, with chemotherapy delivering limited benefit and significant toxicity, and initial Phase 2 data with BDTX-1535 look quite promising,” said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology and Therapeutics Research at City of Hope. “There is a significant unmet medical need for an effective and well-tolerated oral therapy for patients who progress on osimertinib, as well as newly diagnosed patients with non-classical mutations.”
Phase 2 preliminary data overview:
The phase 2 trial began in August of 2023, and enrolled relapsed/refractory patients with non-classical EGFR mutations (NCMs) (Cohort 1) and those with C797S resistance mutations (Cohort 2). Safety assessment and dose selection were based upon the first 40 patients randomized to receive BDTX-1535 once daily at either 100 mg or 200 mg across both Cohorts. Preliminary response rate and durability were assessed in 27 patients at 200 mg with an August 17, 2024, data cutoff, including 22 response-evaluable patients who met protocol eligibility criteria.
Key takeaways:
- 200 mg daily selected for pivotal clinical development. Dose selection was based primarily on pharmacokinetics, safety and tolerability data from 20 patients at 100 mg, and 20 patients at 200 mg.
- Favorable tolerability profile at 200 mg, consistent with prior BDTX-1535 clinical data. The majority of adverse events were mild or moderate, and no new safety signals were observed. The most common on-target treatment-related adverse events were rash (
70% ) and diarrhea (35% ). There were 2 cases of grade 3 rash, and no reported cases of grade 4 rash or grade 3/4 diarrhea. - Preliminary objective response rate (ORR) of
42% achieved in 19 patients. For the 22 response-evaluable patients, the preliminary ORR was36% . Nineteen of these 22 patients expressed known osimertinib resistance mutations: either C797S or P-loop alpha-C helix compressing (PACC, a major subset of NCMs). Of these 19 patients, 8 achieved a response (42% ): 5 with a confirmed partial response (PR), including 1 patient who converted from a PR to an unconfirmed complete response (CR) at 8 months (and awaits confirmatory scan); and 3 with an unconfirmed PR at first scan and awaiting a confirmatory scan. An additional 9 patients experienced stable disease. - Encouraging durability observed, with duration of response (DOR) of approximately 8 months or more for first 3 patients with PR; 14 of 19 patients remain on therapy. Mean follow-up time is 4.7 months.
“We are pleased to see significant Phase 2 clinical activity and tolerability that are consistent with our Phase 1 results,” said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. “We believe that the activity observed in the recurrent setting can translate to robust clinical benefit in the first-line setting, and we look forward to sharing data from our trial in newly diagnosed patients in Q1 2025.”
Black Diamond continues to enroll patients in the second- and third-line cohorts, as well as in the first-line setting for patients with non-classical EGFR mutations. In Q1 2025, the Company expects to disclose initial results from the first-line cohort and to outline potential registrational paths in the recurrent setting based on FDA feedback.
About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic EGFR mutations in NSCLC, including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A “window of opportunity” trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).
About Black Diamond Therapeutics
Black Diamond Therapeutics is a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer. The Company’s MasterKey therapies are designed to address a broad spectrum of genetically defined tumors, overcome resistance, minimize wild-type mediated toxicities, and be brain penetrant to treat central nervous system disease. The Company is advancing two clinical-stage programs: BDTX-1535, a brain-penetrant fourth-generation EGFR MasterKey inhibitor targeting EGFR mutant NSCLC and GBM, and BDTX-4933, a brain-penetrant RAF MasterKey inhibitor targeting KRAS, NRAS and BRAF alterations in solid tumors. For more information, please visit www.blackdiamondtherapeutics.com.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the potential of BDTX-1535 to address the unmet medical need for patients with recurrent NSCLC and for newly diagnosed NSCLC patients with non-classical EGFR mutations and benefit patients with NSCLC across multiple lines of therapy, the continued development and advancement of BDTX-1535, including the ongoing clinical trials and the timing of clinical updates for BDTX-1535 in patients with NSCLC and in patients with recurrent GBM; the expected timing for regulatory feedback and potential registrational pathways for BDTX-1535 in NSCLC; the estimates regarding the market opportunities for the Company’s product candidates; and the potential future development plans for BDTX-1535 in NSCLC. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the United States Securities and Exchange Commission and in its subsequent filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contacts
For Investors:
Mario Corso, Head of Investor Relations, Black Diamond Therapeutics
mcorso@bdtx.com
For Media:
media@bdtx.com
FAQ
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