Augtyro (repotrectinib)

This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment.

The efficacy of tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, lorlatinib, entrectinib, and repotrectinib was systematically evaluated. Our findings underscore that although G2032R and L2026M mutations reside within the kinase active site, their impact extends far beyond steric hindrance, altering overall kinase domain dynamics. Collectively, these data establish a robust panel of patient-derived ROS1 cell lines that recapitulate clinical resistance patterns and, together with complementary computational modeling, provide a valuable framework to dissect ROS1 tumor biology and support rational design of next-generation inhibitors.

The patient was treated with temozolomide concurrently with radiotherapy, followed by tumor treating fields with adjuvant temozolomide...Various tyrosine kinase inhibitors, including entrectinib, larotrectinib, repotrectinib, and selitrectinib, along with bevacizumab, were considered to potentially prolong progression-free survival and overall survival and improve quality of life. We expect to highlight the rarity of this case while discussing the effectiveness of second-generation tyrosine kinase inhibitors in high-grade glioblastomas with rare gene fusions. We also hope to identify the appropriate timeline and treatment sequence for post-standard care, given the lack of official guidelines regarding cases this infrequent.

P=N/A, N=10, Not yet recruiting, Bristol-Myers Squibb

Osimertinib plus repotrectinib showed safety and promising icORR. Results were comparable to new combinations, considering heavily pretreated patients. Efficacy in biomarker-selected NSCLC patients requires further investigation.

TRK inhibitors (larotrectinib, entrectinib, repotrectinib) are FDA/EMA-approved for pediatric and adult solid tumors with NTRK fusions and have demonstrated high and durable response rates. The identification of ETV6-NTRK3 provides diagnostic specificity and offers a precision oncology option in the event of relapse. Long-term surveillance and multidisciplinary follow-up remain essential for optimal care.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

The patient received treatment with crizotinib and entrectinib successively. No new severe drug-related adverse events were observed. This case suggests that in patients with ROS1 fusion-positive nonsmall cell lung cancer who have experienced prior ROS1-tyrosine kinase inhibitor treatment failure and concomitant severe renal insufficiency, repotrectinib may represent a potential and tolerable treatment option when fully assessing clinical risks and ensuring close monitoring.

P1, N=30, Completed, Bristol-Myers Squibb | Recruiting --> Completed

Peripheral monocyte profiling of the patient post-Repotrectinib and localized radiotherapy showed 75% CD8+/CD3 + T cells, 14.2% CD4+/CD3 + T cells, 3.95% regulatory T cells (Tregs), and 38% PD-1 + CD3 + T cells...Furthermore, we also provide a comprehensive review of recent clinical advancements in ALK/ROS1-TKI for NSCLC, including mechanistic insights into TKI resistance development. This case underscores the therapeutic potential of molecular-targeted agents in LUSC and highlights the essential role of NGS-guided precision oncology.