MA07.09 BBT-176, a 4th generation EGFR TKI, for Progressed NSCLC after EGFR TKI Therapy: PK, Safety and Efficacy from Phase 1 Study

Lim, S.M.; Ahn, J.S.; Hong, M.-H.; Kim, T.M.; Jung, H.-A.; Ou, S.-H.I.; Jeong, S.; Lee, Y.-H.; Yim, Eunha; Jung, S.; Lee, S.-Y.; Kim, D.-W.

doi:10.1016/j.jtho.2022.07.118

Cited by 13 publications

(9 citation statements)

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“…These changes were correlated with tumor shrinkage in two of the patients. 28 Two patients with Ex19del/T790M/C797S showed radiological improvements in both target and non-target lesions.…”

Section: Strategies To Overcome Osimertinib Resistancementioning

confidence: 95%

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

et al. 2022

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The discovery of activating mutations in epidermal growth factor receptor (EGFR) in non-small-cell lung cancer transformed the care and prognosis of patients and heralded the era of ‘personalized medicine’ in thoracic oncology. Osimertinib, a third-generation EGFR inhibitor, has been established as the preferred EGFR inhibitor for newly diagnosed patients which urged the need to develop treatment options for patients progressing on first-line osimertinib. However, acquired resistance invariably emerges and numerous efforts have been attempted to delay or overcome acquired resistance. In this article, we thoroughly reviewed the current understanding of osimertinib resistance mechanisms and explored the established and emerging treatment options. Newer treatment strategies targeting EGFR-dependent or -independent resistance mechanisms, novel approaches using bispecific antibodies and antibody–drug conjugates will be discussed. Moreover, what to do with brain only progression, and how to incorporate immunotherapy in EGFR-mutant lung cancer will be discussed. Lastly, future perspectives on the ongoing clinical trials and combination of front-line therapy will be introduced.

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“…These changes were correlated with tumor shrinkage in two of the patients. 28 Two patients with Ex19del/T790M/C797S showed radiological improvements in both target and non-target lesions.…”

Section: Strategies To Overcome Osimertinib Resistancementioning

confidence: 95%

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

et al. 2022

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“… 50 A phase I study of BBT-176 was designed to investigate the tolerability and antitumor activity in patients with EGFR mutations who were previously treated with at least one line of EGFR-TKI therapy (NCT04820023). 51 The interim results showed that among 18 enrolled patients, 5 harbored a triple-mutant EGFR gene (exon19del/T790M/C797S or L858R/T790M/C797S). Toxicities were well tolerated, and no treatment discontinuation or dose-limiting toxicity occurred.…”

Section: Bbt-176mentioning

confidence: 98%

Novel systemic therapies in the management of tyrosine kinase inhibitor-pretreated patients with epidermal growth factor receptor-mutant non-small-cell lung cancer

Li,

Jie,

2023

Ther Adv Med Oncol

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line option for non-small-cell lung cancer (NSCLC) harboring active EGFR mutations. The overall survival of patients with advanced NSCLC has improved dramatically with the development of comprehensive genetic profiles and targeted therapies. However, resistance inevitably occurs, leading to disease progression after approximately 10–18 months of EGFR-TKI treatment. Platinum-based chemotherapy is the standard treatment for patients who have experienced disease progression while undergoing EGFR-TKI treatment, but its efficacy is limited. The management of extensively pretreated patients with EGFR-mutant NSCLC is becoming increasingly concerning. New agents have shown encouraging efficacy in clinical trials for this patient population, including fourth-generation EGFR-TKIs, EGFR-TKIs combined with counterpart targeted drugs, and novel agents such as antibody–drug conjugates. We review current efforts to manage extensively pretreated patients with EGFR-mutant NSCLC.

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“…Nevertheless, lung cancer patients treated with osimertinib eventually develop acquired resistance, which is characterized by different mechanisms, either according to EGFR-dependent or EGFR-independent pathways [ 11 , 16 , 17 , 18 ]. To address this acquired resistance, developing BBT-176 as a fourth-generation EGFR TKI is considered effective against the C797S mutation, which confers resistance to third-generation TKIs [ 19 ]. Combination strategies are undergoing preclinical and clinical investigations to address EGFR TKI resistance.…”

Section: Targeted Therapiesmentioning

confidence: 99%

Cutting-Edge Therapies for Lung Cancer

La’ah,

Chiou

2024

Cells

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Lung cancer remains a formidable global health challenge that necessitates inventive strategies to improve its therapeutic outcomes. The conventional treatments, including surgery, chemotherapy, and radiation, have demonstrated limitations in achieving sustained responses. Therefore, exploring novel approaches encompasses a range of interventions that show promise in enhancing the outcomes for patients with advanced or refractory cases of lung cancer. These groundbreaking interventions can potentially overcome cancer resistance and offer personalized solutions. Despite the rapid evolution of emerging lung cancer therapies, persistent challenges such as resistance, toxicity, and patient selection underscore the need for continued development. Consequently, the landscape of lung cancer therapy is transforming with the introduction of precision medicine, immunotherapy, and innovative therapeutic modalities. Additionally, a multifaceted approach involving combination therapies integrating targeted agents, immunotherapies, or traditional cytotoxic treatments addresses the heterogeneity of lung cancer while minimizing its adverse effects. This review provides a brief overview of the latest emerging therapies that are reshaping the landscape of lung cancer treatment. As these novel treatments progress through clinical trials are integrated into standard care, the potential for more effective, targeted, and personalized lung cancer therapies comes into focus, instilling renewed hope for patients facing challenging diagnoses.

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MA07.09 BBT-176, a 4th generation EGFR TKI, for Progressed NSCLC after EGFR TKI Therapy: PK, Safety and Efficacy from Phase 1 Study

Cited by 13 publications

References 0 publications

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

Novel systemic therapies in the management of tyrosine kinase inhibitor-pretreated patients with epidermal growth factor receptor-mutant non-small-cell lung cancer

Cutting-Edge Therapies for Lung Cancer

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