^
2d
Complex dyslipidemia induced by Lorlatinib therapy: A case study. (PubMed, J Clin Lipidol)
Lorlatinib induced a complex dyslipidemia in our patient with elevations of both LDL-C and HDL-C. The underlying mechanism of lorlatinib-induced hyperlipidemia remains unknown and is unlikely to be secondary to nephrotic syndrome in many patients.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
3d
Lorlatinib in the second line and beyond for ALK positive lung cancer: real-world data from resource-constrained settings. (PubMed, BJC Rep)
This real-world data confirms the efficacy of Lorlatinib in the second line and beyond with adverse effects matching that of registration studies.
Journal • Real-world evidence • Real-world
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
3d
Lorlatinib overcomes alectinib-induced hemolytic anemia in an ALK fusion positive non-small-cell lung cancer patient with severe tumor-associated liver failure: A case report. (PubMed, Thorac Cancer)
In this case, lorlatinib effectively controlled the tumor and improved the patient's liver function and performance status. This case highlights the importance of adapting treatment strategies to manage adverse effects while ensuring the continued use of ALK inhibitors for optimal patient outcomes.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion
|
Alecensa (alectinib) • Lorbrena (lorlatinib)
3d
COMLORLA: Real-world Study of Local Therapy Changes During 1L Lorlatinib in Unresectable ALK+ NSCLC (clinicaltrials.gov)
P=N/A, N=100, Not yet recruiting, Peking University Cancer Hospital & Institute
New trial • Real-world evidence • Real-world
|
ALK (Anaplastic lymphoma kinase)
|
Lorbrena (lorlatinib)
5d
New P1 trial
|
APG-2449
6d
New P2 trial
|
Lorbrena (lorlatinib)
6d
Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer (clinicaltrials.gov)
P4, N=71, Completed, Pfizer | Active, not recruiting --> Completed
Trial completion
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Lorbrena (lorlatinib)
10d
Trial initiation date • Real-world evidence • Real-world
|
Lorbrena (lorlatinib)
11d
New trial • Real-world evidence • Real-world effectiveness • Real-world
|
Lorbrena (lorlatinib)
19d
Long-Term Response of Lorlatinib to Leptomeningeal Metastasis in Patients with Anaplastic Lymphoma Kinase Fusion Positive Non-Small Lung Cancer: A Case Report. (PubMed, Case Rep Oncol)
In further analysis, lorlatinib revealed superior intracranial efficacy and prolonged time to intracranial progression compared with crizotinib. Herein, we report a case of ALK-positive NSCLC with leptomeningeal metastasis that was successfully treated with lorlatinib after progression to brigatinib and alectinib. This case demonstrates the potential of lorlatinib in managing leptomeningeal metastasis in ALK-positive NSCLC. The case suggests a paradigm shift in therapeutic approaches for CNS metastasis, including brain and leptomeningeal metastases.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement • ALK fusion
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
23d
Gene-expression profile analysis to disclose diagnostics and therapeutics biomarkers for thyroid carcinoma. (PubMed, Comput Biol Chem)
Then we detected 6 repurposable drug molecules (Entrectinib, Imatinib, Ponatinib, Sorafenib, Retevmo, and Pazopanib) by molecular docking with KGs-mediated receptor proteins, ADME/T analysis, and cross-validation with the independent receptors. Therefore, these findings might be useful resources for wet lab researchers and clinicians to consider an effective treatment strategy against THCA.
Journal • Gene Expression Profile
|
TOP2A (DNA topoisomerase 2-alpha) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • RUNX2 (RUNX Family Transcription Factor 2)
|
KIM1 expression • TIMP1 expression
|
sorafenib • Rozlytrek (entrectinib) • imatinib • Iclusig (ponatinib) • pazopanib • Retevmo (selpercatinib)
25d
Trial initiation date
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
Augtyro (repotrectinib)
27d
New trial • Adverse events • Real-world evidence • Real-world • Metastases
|
Lorbrena (lorlatinib)
28d
Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report. (PubMed, Heliyon)
After the initial treatment with ensartinib, the patient experienced intracranial disease progression...Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib...Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away...Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4)
|
TP53 mutation • ALK fusion • ALK mutation • EML4-ALK variant 3 + TP53 mutation • ALK fusion + EML4-ALK variant 3 + TP53 mutation
|
Keytruda (pembrolizumab) • Lorbrena (lorlatinib) • Ensacove (ensartinib)
1m
Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions. (PubMed, Cancers (Basel))
Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases...More recently, the FDA approved the use of repotrectinib, a second-generation TRK inhibitor, in patients with NTRK fusions, based on data suggesting clinical efficacy and safety, which could offer another tool for the treatment of NTRK-altered cancers. In this review, we summarize the current evidence related to the use of TRK inhibitors in the tissue-agnostic setting. We also elaborate on the safety profiles and resistance mechanisms from a practical perspective.
Review • Journal • Pan tumor
|
NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK fusion
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
1m
New trial • Metastases
|
Qi Xinke (iruplinalkib)
1m
In-depth theoretical modeling to explore the mechanism of TPX-0131 overcoming lorlatinib resistance to ALKL1196M/G1202R mutation. (PubMed, Comput Biol Med)
The tight binding of TPX-0131 to residues Arg1202, Met1199 and Arg1120 contribute significantly to overcoming lorlatinib resistance in ALKL1196M/G1202R mutant. These research results are expected to offer insights into the mechanism of TPX-0131 in treating ALKG1202R/L1196M-induced NSCLC resistance and optimizing of ALK inhibitors.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK mutation • ALK G1202R • ALK L1196M
|
Lorbrena (lorlatinib) • TPX-0131
1m
Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer. (PubMed, Clin Transl Med)
The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 fusion • ROS1 positive • ROS1 rearrangement • ROS1 G2032R
|
Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
1m
Lorlatinib Continuation Study (clinicaltrials.gov)
P4, N=73, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=200 --> 73
Enrollment closed • Enrollment change
|
Lorbrena (lorlatinib)
1m
Response to Crizotinib After Entrectinib Resistance in ROS1-Rearranged, MET-Amplified Lung Adenocarcinoma. (PubMed, JCO Precis Oncol)
Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ROS1 rearrangement • ROS1 amplification
|
Xalkori (crizotinib) • Rozlytrek (entrectinib)
1m
Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC). (PubMed, Lung Cancer)
Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.
Retrospective data • Review • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
2ms
Early prediction and impact assessment of CYP3A4-related drug-drug interactions for small molecule anti-cancer drugs using human-CYP3A4-transgenic mouse models. (PubMed, Drug Metab Dispos)
Victim drugs brigatinib and lorlatinib were evaluated with the new approach in combination with the perpetrator drugs itraconazole and rifampicin. The model was able to adequately describe the inhibition of CYP3A4 metabolism and the subsequent magnitude of change in exposure. However, it was unable to accurately predict the magnitude of change in exposure of victim drugs in combination with an inducer.
Preclinical • Journal
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
Lorbrena (lorlatinib) • Alunbrig (brigatinib) • itraconazole • rifampicin
2ms
Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations. (PubMed, J Med Chem)
On-target mutations of the ROS1 kinase domain confer resistance to crizotinib and lorlatinib in more than one-third of acquired resistance cases with no current effective treatment option. The degrader can effectively inhibit ROS1-dependent cell proliferation and tumor growth by degrading the ROS1 kinase, thereby eliminating the active phospho-ROS1. More importantly, the degradation-based therapeutic modality can overcome on-target mutation resistance to tyrosine kinase inhibitors by efficient degradation of the mutated kinase to achieve greater potency than inhibition.
Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 fusion
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
2ms
Plain language summary: 5-year results from the CROWN study of lorlatinib vs crizotinib in non-small-cell lung cancer. (PubMed, Future Oncol)
The 5-year results from the CROWN study showed that more people who took lorlatinib continued to benefit from their treatment than those who took crizotinib. The 5-year benefit of lorlatinib in people with ALK-positive NSCLC has never been seen before.Clinical Trial Registration: NCT03052608 (Phase 3 CROWN study) (ClinicalTrials.gov).
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
2ms
Enrollment open
|
Augtyro (repotrectinib)
2ms
Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial. (PubMed, Target Oncol)
In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.
Retrospective data • Journal
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK positive • NTRK fusion
|
Rozlytrek (entrectinib)
2ms
ALKTERNATE: A Pilot Study Alternating Lorlatinib With Crizotinib in ALK-Positive NSCLC With Prior ALK Inhibitor Resistance. (PubMed, JTO Clin Res Rep)
Results support progressing inquiry into this approach and propose a flexible design with drug(s) selected and alternating time frames, informed by real-time plasma profiling. Moving this concept to treatment naive may also optimize impact.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • ALK positive
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
2ms
Association between lorlatinib blood concentration and adverse events and clinical impact of dose modification. (PubMed, Lung Cancer)
Dose modification of lorlatinib was associated with successful management of AEs and decreased serum concentration of lorlatinib.
Journal • Adverse events
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Lorbrena (lorlatinib)
2ms
Application of newly developed and validated UPLC-MS/MS method for pharmacokinetic study of ROS1/NTRK inhibitor taletrectinib in beagle dog plasma. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci)
The procedure was then applied to quantify taletrectinib in beagle dog plasma after oral and intravenous doses and achieved success. The obtained pharmacokinetic parameters indicated high bioavailability of taletrectinib (>85 %) and extensive tissue distribution (>40 L/kg).
PK/PD data • Journal
|
NTRK (Neurotrophic receptor tyrosine kinase)
|
taletrectinib (AB-106)
2ms
New P4 trial • Real-world evidence • Real-world • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Qi Xinke (iruplinalkib)
2ms
Current Landscape of NTRK Inhibition for Pediatric CNS Tumors. (PubMed, CNS Drugs)
The use of larotrectinib and entrectinib in the relapsed setting for pediatric CNS tumors has resulted in rapid and robust responses in an important fraction of patients. As these agents are more broadly used, resistance will become a more pervasive issue and strategies will need to be determined for this scenario. This article summarizes the current status of NTRK inhibitors for pediatric CNS tumors and discusses the opportunities and challenges of their expanding use in the future.
Journal
|
NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK positive • NTRK fusion
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
2ms
New findings on the incidence and management of CNS adverse reactions in ALK-positive NSCLC with lorlatinib treatment. (PubMed, Discov Oncol)
CNS adverse reactions frequently occur in ALK-positive NSCLC patients on lorlatinib, yet they are reversible with appropriate management. Research should continue to optimize treatment protocols to decrease these reactions' frequency.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
2ms
Lorlatinib in the treatment of a rare pulmonary mucoepidermoid carcinoma with EML4-ALK fusion: a case report and literature review. (PubMed, Front Oncol)
The patient was treated with lorlatinib as the first-line treatment. This case is the first to describe the effectiveness of lorlatinib in treating an advanced high-grade PMEC with EML4-ALK fusion V2 mutation patient.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
EML4-ALK fusion • ALK fusion • ALK mutation
|
Lorbrena (lorlatinib)
2ms
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations. (PubMed, Cancer Discov)
These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion-positive non-small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations. Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion • ALK mutation • ALK G1202R
|
Lorbrena (lorlatinib) • NVL-655
2ms
ROS1-rearranged non-small cell lung cancer: Understanding biology and optimizing management in the era of new approvals. (PubMed, Curr Probl Cancer)
Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.
Review • Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 rearrangement
|
Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
2ms
Unusual presentation of ROS1 rearranged metastatic non-small cell lung cancer. (PubMed, Respir Med Case Rep)
The patient was ultimately diagnosed with ROS1 rearranged lung adenocarcinoma and achieved a dramatic response with entrectinib. This case highlights the variable presentation of non-small cell lung cancer (NSCLC) and the importance of comprehensive molecular testing for newly diagnosed metastatic NSCLC.
Journal • Metastases
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 rearrangement
|
Rozlytrek (entrectinib)
2ms
Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-type Non-Small Cell Lung Cancer. (PubMed, Cancer Res)
Notably, suppression of the NTRK1 pathway by knockdown or Entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models...RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating crosstalk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcomes immunotherapy resistance in NTRK1 wild-type NSCLC patients.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
|
Rozlytrek (entrectinib)
2ms
Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons. (PubMed, Clin Lung Cancer)
Lorlatinib was estimated to have superior efficacy over first- and second-generation ALK-TKIs, but a higher rate of Grade ≥3 AEs compared to alectinib. These data support the use of lorlatinib as a first-line treatment for ALK+ advanced/metastatic NSCLC.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
3ms
DELINOR: A Study to Learn About the Effectiveness of Cancer Medicines in Patients With Metastatic Non-small Cell Lung Cancer in Norway. (clinicaltrials.gov)
P=N/A, N=1, Completed, Pfizer | Recruiting --> Completed | N=20605 --> 1 | Trial completion date: Feb 2025 --> Jan 2024 | Trial primary completion date: Feb 2025 --> Jan 2024
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • erlotinib • Gilotrif (afatinib) • carboplatin • gefitinib • Rozlytrek (entrectinib) • paclitaxel • docetaxel • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Vizimpro (dacomitinib)
3ms
A Study to Learn About the Study Medicine (Called Lorlatinib) in People With Liver Dysfunction (clinicaltrials.gov)
P1, N=21, Completed, Pfizer | Active, not recruiting --> Completed | N=16 --> 21
Trial completion • Enrollment change
|
Lorbrena (lorlatinib)
3ms
Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study). (PubMed, Curr Oncol)
Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.
Retrospective data • Journal • Real-world evidence • Real-world
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
Metastatic Non-Myofibroblastic Sarcoma Harbouring EML4-ALK Fusion-Dramatic Response to ALK Tyrosine Kinase Inhibitors and Development of Resistance Mutations. (PubMed, Cancer Rep (Hoboken))
This case report adds to a body of evidence demonstrating the potential transformative response to targeted therapy in non-lung solid organ tumours harbouring ALK fusions. This is the first description tracking the development of resistance mutations in a patient with non-myofibroblastic sarcoma and questions the utility of the presence of G1202R mutation as a marker of lorlatinib sensitivity in non-lung ALK rearranged tumours, contrary to experience in lung cancer.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
Alecensa (alectinib) • Lorbrena (lorlatinib) • doxorubicin hydrochloride