Rozlytrek (entrectinib) / Roche, Nerviano Medical Sciences - LARVOL DELTA

SHEDDING LIGHT ON PATIENT-REPORTED OUTCOME MEASURE UTILIZATION ACROSS NSCLC THERAPIES (ISPOR 2026) - "Within monotherapies, disease-specific quality-of-life (QOL) measures, particularly EORTC QLQ-C30 (n=11) and EORTC QLQ-LC13 (n=8), were frequently used in trials of ALK inhibitors (e.g., alectinib), PD-L1 inhibitors (e.g., atezolizumab, durvalumab), and PD-1 inhibitors (e.g., nivolumab, and pembrolizumab). Tyrosine kinase inhibitors (e.g., zongertinib, entrectinib) combined disease-specific EORTC QLQ-C30 and generic QOL instruments, such as EQ-5D (n= 4). In contrast, TIGIT inhibitors (e.g. rilvegostomig) and antibody-drug conjugates (e.g. dato-DXd) predominantly utilize PROMIS, which assesses general health and physical and mental functioning rather than QOL (n= 4). PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. Substantial heterogeneity in PRO instrument selection suggests a lack of..."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT

SHEDDING LIGHT ON PATIENT-REPORTED OUTCOME MEASURE UTILIZATION ACROSS NSCLC THERAPIES (ISPOR 2026) - "Within monotherapies, disease-specific quality-of-life (QOL) measures, particularly EORTC QLQ-C30 (n=11) and EORTC QLQ-LC13 (n=8), were frequently used in trials of ALK inhibitors (e.g., alectinib), PD-L1 inhibitors (e.g., atezolizumab, durvalumab), and PD-1 inhibitors (e.g., nivolumab, and pembrolizumab). Tyrosine kinase inhibitors (e.g., zongertinib, entrectinib) combined disease-specific EORTC QLQ-C30 and generic QOL instruments, such as EQ-5D (n= 4). In contrast, TIGIT inhibitors (e.g. rilvegostomig) and antibody-drug conjugates (e.g. dato-DXd) predominantly utilize PROMIS, which assesses general health and physical and mental functioning rather than QOL (n= 4). PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. Substantial heterogeneity in PRO instrument selection suggests a lack of..."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT

Congenital mesoblastic nephroma: a single-center retrospective study. (PubMed, Transl Pediatr) - "Two relapsed patients received salvage chemotherapy [vincristine-actinomycin D-cyclophosphamide (VAC) or ifosfamide-carboplatin-etoposide (ICE)], which showed limited efficacy. One relapsed patient with TPM3::NTRK1 received larotrectinib but died two months later; another with EGFR-KDD experienced disease stabilization after afatinib plus programmed cell death protein 1 (PD-1) blockade following progression on entrectinib and anlotinib...While most patients experienced favorable outcomes following surgery, relapsed cases highlight the challenges associated with molecularly atypical disease. These observations are descriptive in nature and underscore the need for larger collaborative studies to better define prognostic factors and optimal management strategies in CMN."

IO biomarker • Journal • Retrospective data • Kidney Cancer • Oncology • Pediatrics • Renal Cell Carcinoma • Solid Tumor • EGFR • ETV6 • NTRK1 • NTRK3 • TPM3

Primary endpoint of ROSALINE: A phase II neoadjuvant study of endocrine therapy (ET) and entrectinib in invasive lobular breast carcinoma (ILBC) (ESMO-BC 2025) - P2 | "ROSALINE is the first neoadjuvant trial focused on ILBC, evaluating ET and entrectinib in HR+/HER2- disease. This investigator-initiated, single-arm, phase II trial enrolled women with stage IIA–IIIA HR+/HER2– ILBC treated with 4 cycles of letrozole (2.5 mg/day) + entrectinib (600 mg/day), + goserelin for premenopausal women, followed by surgery. The primary endpoint was not met and dose reductions were frequent. However, neoadjuvant entrectinib with ET showed activity. Correlative analyses are ongoing to clarify role of ROS1 inhibition in ILBC and identify predictive biomarkers."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDH1 • HER-2

Efficacy of lorlatinib after failure of a first-line ROS1 tyrosine kinase inhibitor (ROS1 TKI) in patients (pts) with advanced ROS1-positive non-small cell lung cancer (ROS1+ NSCLC) (IFCT-2003 ALBATROS) (ESMO 2025) - P2 | "Background Current ESMO guidelines recommend ROS1 TKIs crizotinib and entrectinib as preferred first-line treatments for advanced ROS1 + NSCLC. Conclusions In this phase II trial, lorlatinib demonstrated robust clinical activity in ROS1+ NSCLC pts who received one line of ROS1+ TKI, mostly crizotinib. Lorlatinib activity according to baseline molecular profile including resistance mutation to crizotinib will be presented."

Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Intragenic fusion architecture dictates resistance: UGT1A1 links CD74-ROS1 breakpoint heterogeneity to TKI response (ELCC 2026) - "The molecular mechanism underlying this variant-specific intrinsic resistance remains completely unknown, representing a major gap in knowledge that impedes personalized therapeutic strategies.Methods To elucidate the mechanism, we established isogenic NSCLC cell models expressing CR-L or CR-S and systematically evaluated their in vitro sensitivity (IC50) to multiple ROS1 TKIs (crizotinib, entrectinib, and lorlatinib). We identify UGT1A1-mediated metabolism as a novel, variant-specific resistance mechanism in CR-L NSCLC-a new paradigm distinct from acquired mutations. Our findings nominate UGT1A1 as a predictive biomarker and establish a directly translatable combinatorial strategy (atazanavir + lorlatinib) to overcome this primary resistance."

Heterogeneity • Lung Cancer • Non Small Cell Lung Cancer • CD74 • ROS1 • UGT1A1

Skeletal muscle, subcutaneous and intramuscular fat as prognostic biomarkers in TKI-treated fusion-positive NSCLC (ELCC 2026) - "BC parameters were correlated to progression-free survival (PFS) using a Cox model.Results Among 17 pts, 10 ALK positive pts were treated with alectinib and 4 with lorlatinib, while 2 ROS1-positive and 1 NTRK1-positive with entrectinib. Notably, SAT was also related to worse PFS at all time points: T0 (HR 1.02; p=0.046), T1 (HR 1.02; p=0.040), T2 (HR 1.02; p=0.023), and T3 (HR 1.02; p=0.043). No statistically significant changes in BC parameters were observed across time-points (T0-T3), possibly due to the nutritional intervention and limited sample size.Conclusions Despite the preliminary nature of these findings, SMA, SAT and IMAT emerged as potential prognostic biomarkers in fusion-positive NSCLC pts treated with TKIs, highlighting the clinical relevance of body composition assessment and suggesting a pivotal role of targeted interventions, including nutritional support and physical exercise."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • NTRK1 • ROS1

Taletrectinib, a next generation selective ROS1 inhibitor, demonstrates a differentiated profile in ROS1 fusion models (AACR 2026) - "FDA-approved tyrosine kinase inhibitors (TKI) for ROS1 fusion positive NSCLC include crizotinib, entrectinib, repotrectinib, and more recently, taletrectinib. Taletrectinib treatment also induced tumor regressions in several in vivo ROS1 fusion models, regardless of the fusion partner. In summary, our nonclinical data demonstrate that, at clinically relevant concentrations, taletrectinib exhibits activity in ROS1 wild-type and mutant-driven cancers and has a distinct profile that addresses the unmet needs of ROS1-positive NSCLC patients."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK2

Novel inhibitors of BCRP and P-gp found among drugs used in the treatment of cancer (AACR 2026) - "Of the investigated compounds, cabozantinib (IC50 of 0.65 µM), midostaurin (0.69 µM), and entrectinib (5.8 µM) showed the strongest inhibition of BCRP. Nilotinib (1.0 µM), osimertinib (2.0 µM), and abemaciclib (2.4 µM) showed the strongest inhibition of the P-gp. The highest I2/IC50 ratios for BCRP were observed for mitotane (6190), cabozantinib (1730), and abiraterone (831). For P-gp, the highest I2/IC50 ratios were observed for nilotinib (2880), pazopanib (1580), and mitotane (1480)...The highest I1/IC50 ratios for BCRP were observed for doxorubicin (8.2), etoposide (2.8), and fosaprepitant (0.84). For P-gp, the highest I1/IC50 ratios were observed for amscarine (1.6), vinorelbine (0.55), and fosaprepitant (0.50)...Mechanistic static model for BCRP inhibitors suggested that cabozantinib, midostaurin, and apalutamide could almost fully inhibit intestinal BCRP, increasing the exposure to concomitantly administered rosuvastatin by 94%, 89%,..."

Breast Cancer • Oncology • Solid Tumor

Entrectinib-Induced Sinus Bradycardia in a Patient With Metastatic Non-Small Cell Lung Cancer. (PubMed, JACC Case Rep) - "Sinus bradycardia may be a rare but significant side effect of entrectinib, possibly related to ALK inhibition. Cardiac monitoring and multidisciplinary management are essential when initiating therapy with ALK/ROS1 inhibitors."

Journal • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Regulatory divergence in EMA approvals for targeted therapies in oncogene addicted NSCLC (ESMO-TAT 2026) - "Investigation of the factors behind divergent regulatory outcomes could help clarify the regulatory pathway for future drugs targeting molecularly-defined subsets of NSCLC. Comparative review of CHMP/EC documents and EPARs for crizotinib (Xalkori®), entrectinib (Rozlytrek®), repotrectinib (Augtyro®), sotorasib (Lumykras®), adagrasib (Krazati®), selpercatinib (Retsevmo®), pralsetinib (Gavreto®), trastuzumab deruxtecan (Enhertu®), tepotinib (Teptmeko®) and capmatinib (Tabrecta®). EMA approvals for oncogene-addicted NSCLC show inconsistency across biomarkers. A clear and consistent application of a framework for small-population settings is essential to (1) define when ORR/DoR benchmarks from robust single-arm studies justify line-agnostic approval; (2) align post-authorisation obligations to residual uncertainty; and (3) enable a similar developmental approach to first- and later line targeted therapies that address unmet..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • MET • ROS1

WHEN TARGETED THERAPY TARGETS THE HEART: A CASE OF ENTRECTINIB INDUCED CARDIOTOXICITY (ACC 2026) - "We presented a patient who developed new-onset heart failure (HF) following initiation of entrectinib. Symptoms worsened despite standard HF treatment. Discontinuing entrectinib and giving intravenous steroids led to marked clinical improvement."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

Clinical and molecular characteristics of NTRK fusion–positive solid tumors treated with entrectinib: An international multicenter retrospective real-world cohort study (Sarcoma-RC 2026) - "Legal entity responsible for the study The authors. Funding Has not received any funding."

Real-world • Real-world evidence • Retrospective data • Brain Cancer • CNS Tumor • Lung Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NTRK • NTRK1 • NTRK2 • NTRK3

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2024 ➔ Aug 2028 | Trial primary completion date: Apr 2024 ➔ Aug 2028

Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • IO Companion diagnostic • PD(L)-1 companion diagnostic • Tumor mutational burden • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2022 ➔ Sep 2020

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ Mar 2020

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Mar 2020 ➔ Sep 2020

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=660 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ Sep 2021 | Trial primary completion date: Sep 2020 ➔ Sep 2021

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | N=700 ➔ 1000

Enrollment change • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Not yet recruiting | Sponsor: Hoffmann-La Roche

IO Companion diagnostic • New P2/3 trial • PD(L)-1 companion diagnostic • Tumor mutational burden • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=700 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2021 ➔ Apr 2024 | Trial primary completion date: Sep 2021 ➔ Apr 2024

Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Feb 2020 ➔ Jun 2019

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial primary completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=580 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jun 2019 ➔ Sep 2020

IO Companion diagnostic • PD(L)-1 companion diagnostic • Trial primary completion date • Tumor mutational burden • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF