^
5d
Lorlatinib After Failure of First-line TKI in Patients with Advanced ROS1-positive NSCLC (ALBATROS) (clinicaltrials.gov)
P2, N=54, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Recruiting --> Active, not recruiting | N=84 --> 54 | Trial completion date: Jan 2026 --> Feb 2027
Enrollment closed • Enrollment change • Trial completion date
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 rearrangement
|
Lorbrena (lorlatinib)
6d
Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=12, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
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TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • MAPK1 (Mitogen-activated protein kinase 1) • NTRK (Neurotrophic receptor tyrosine kinase) • MAPK3 (Mitogen-Activated Protein Kinase 3)
|
TP53 mutation
|
Rozlytrek (entrectinib) • Inqovi (decitabine/cedazuridine)
6d
New P3 trial
|
Lorbrena (lorlatinib)
8d
Addressing challenges with Matching-Adjusted Indirect Comparisons to demonstrate the comparative effectiveness of entrectinib in metastatic ROS-1 positive Non-Small Cell Lung Cancer. (PubMed, BMC Med Res Methodol)
To the best of our knowledge, we present the first in-depth application of QBA in the context of MAIC. Despite the real-world data limitations, with this MAIC, we show that it is possible to confirm the robustness of the results by using appropriate statistical methods.
Journal • HEOR
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 positive
|
Rozlytrek (entrectinib)
8d
First-line lorlatinib versus crizotinib in Asian patients with advanced ALK-positive NSCLC: 5-year outcomes from the CROWN study. (PubMed, J Thorac Oncol)
After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
11d
Entrectinib can induce nerve cell damage by inhibiting PI3K-AKT and TGF-β signaling pathways. (PubMed, Front Pharmacol)
These results identified a critical role of entrectinib in promoting nerve cell damage by downregulating the expression of THBS1 while also inhibiting PI3K-AKT and TGF-β signaling pathways. Our findings will provide potential therapeutic targets for CNS-related toxicities.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • TGFB1 (Transforming Growth Factor Beta 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
ROS1 positive
|
Rozlytrek (entrectinib)
12d
Enrollment open
|
APG-2449
12d
APG-2449 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=150, Recruiting, Ascentage Pharma Group Inc. | Trial completion date: Feb 2025 --> Jan 2028 | Trial primary completion date: Jan 2025 --> Dec 2027
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK positive • ROS1 fusion • ROS1 positive
|
APG-2449
12d
Neoadjuvant WX-0593 in Resectable ALK-positive or ROS1-positive Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=26, Recruiting, Pingping Song | Not yet recruiting --> Recruiting | Trial completion date: Jul 2025 --> Apr 2028 | Trial primary completion date: Mar 2025 --> Jan 2026
Enrollment open • Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK positive • ROS1 positive
|
Qi Xinke (iruplinalkib)
15d
New trial
|
Dovbleron (taletrectinib)
18d
TGRX-326-1004: TGRX-326 Pharmacokinetic Mass Balance (clinicaltrials.gov)
P1, N=6, Completed, Shenzhen TargetRx, Inc. | Not yet recruiting --> Completed
Trial completion
|
deulorlatinib (TGRX-326)
19d
Lorlatinib for Newly-Diagnosed High-Grade Glioma with ROS or ALK Fusion (clinicaltrials.gov)
P1, N=15, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Sep 2034 --> Jun 2035 | Initiation date: Sep 2024 --> Jun 2025 | Trial primary completion date: Sep 2027 --> Jun 2028
Trial completion date • Trial initiation date • Trial primary completion date
|
ALK fusion • ROS1 fusion
|
carboplatin • Lorbrena (lorlatinib) • cyclophosphamide
20d
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) (clinicaltrials.gov)
P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial primary completion date: Dec 2024 --> Dec 2025
Trial primary completion date
|
ALK fusion • ALK mutation • ALK translocation
|
Lorbrena (lorlatinib) • cyclophosphamide • topotecan • Neulasta (pegfilgrastim) • Neupogen (filgrastim)
21d
Crizotinib Treatment for Lorlatinib-resistant MET-amplified EML4-ALK-fusion Positive Advanced Lung Adenocarcinoma: A Case Report (PubMed, Zhongguo Fei Ai Za Zhi)
The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice..
Journal
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4)
|
ALK positive • MET amplification • ALK fusion
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
23d
Post Marketing Surveillance(PMS) Study of Lorviqua in Korea (clinicaltrials.gov)
P=N/A, N=600, Recruiting, Pfizer | Trial completion date: Aug 2028 --> Mar 2028 | Trial primary completion date: Aug 2028 --> Mar 2028
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
24d
Tumor Mutation Burden Survey of AACR GENIE Database Revealed NTRK (NTRK+) and RET (RET+) Fusions Positive Colorectal Carcinoma (CRC) as Distinct Subsets. (PubMed, Cancer Med)
NRTK+ and RET+ CRC possess significantly higher TMB than other RTK+ CRC or NTRK+/RET+ non-CRC solid tumors. TMB testing should be routinely done in MSI-H CRC, and TMB ≥ 35 mut/MB samples should be screened for NTRK and RET fusions as an enrichment strategy to provide additional treatment for NTRK+ and RET+ CRC patients.
Journal • Tumor mutational burden • MSi-H Biomarker
|
TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • NTRK (Neurotrophic receptor tyrosine kinase)
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TMB-H • MSI-H/dMMR • RET fusion • RET mutation • NTRK fusion
|
Rozlytrek (entrectinib) • Retevmo (selpercatinib)
25d
Iruplinalkib for G1202R-mutant non-small cell lung cancer with anaplastic lymphoma kinase double fusion failed to alectinib: a case report. (PubMed, Anticancer Drugs)
The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK-rearranged NSCLC patients with G1202R resistance mutation.
Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK rearrangement • ALK mutation • ALK G1202R
|
Alecensa (alectinib) • Qi Xinke (iruplinalkib)
27d
A Study of IBI363 in Combination With Bevacizumab or Furuitinib in Subjects With Advanced Colorectal Cancer (clinicaltrials.gov)
P1, N=260, Recruiting, Wuhan Union Hospital, China | Active, not recruiting --> Recruiting | N=49 --> 260 | Trial completion date: Jul 2025 --> Jul 2026
Enrollment open • Enrollment change • Trial completion date
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Avastin (bevacizumab) • foritinib (SAF-189)
1m
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
1m
Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report. (PubMed, Oncotarget)
Combination therapy targeting RET and ROS1 using pralsetinib and lorlatinib achieved a partial response with limited durability of only four months. This is the first reported case of a RET fusion as a potential mechanism of resistance to lorlatinib, it identifies a novel RET fusion partner, and it emphasizes the importance of testing for acquired resistance mutations with both DNA and RNA at the time of progression in patients with targetable oncogenic drivers.
Journal
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RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD74 (CD74 Molecule)
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RET fusion • ROS1 fusion • ROS1 rearrangement • RET rearrangement
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Lorbrena (lorlatinib) • Gavreto (pralsetinib)
1m
Kinome reprogramming of G2/M kinases and repression of MYCN contribute to superior efficacy of lorlatinib in ALK-driven neuroblastoma. (PubMed, Mol Cancer Ther)
Mutations in the tyrosine kinase domain of the Anaplastic Lymphoma Kinase (ALK) oncogene in neuroblastoma occur most frequently at one of three hotspot amino acid residues, with the F1174* and F1245* variants conferring de novo resistance to first and second generation ALK inhibitors including crizotinib and ceritinib. Lorlatinib treatment also led to the repression of MYCN expression and its occupancy at promoters of the same G2/M kinases. These data providing mechanistic insight into the superior efficacy of lorlatinib over crizotinib for the treatment of ALK-driven neuroblastoma.
Journal
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ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN expression
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Xalkori (crizotinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib)
1m
Therapeutic benefit of the dual ALK/FAK inhibitor ESK440 in ALK-driven neuroblastoma. (PubMed, Neoplasia)
In certain NB models, ESK440 showed comparable or enhanced efficacy to lorlatinib, another clinical ALK inhibitor, and a lorlatinib-resistant cell line (COG-N-561 LR) retained sensitivity to ESK440. These preclinical results indicate that ESK440 is a promising targeted agent for ALK-driven NB and support future clinical studies to evaluate its efficacy in NB patients.
Journal • IO biomarker
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ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
ALK mutation
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Lorbrena (lorlatinib)
1m
Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review. (PubMed, Jpn J Clin Oncol)
In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability...NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies...However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.
Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker
|
TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK (Neurotrophic receptor tyrosine kinase)
|
TMB-H • MSI-H/dMMR • NTRK positive • NTRK fusion
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Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
1m
Diabetic Ketoacidosis During Lorlatinib Treatment: Case Report. (PubMed, J Thorac Oncol)
We present the case of a 65-year-old male patient with anaplastic lymphoma kinase-positive lung cancer and preexisting type 2 diabetes mellitus who developed diabetic ketoacidosis (DKA) after switching from alectinib to lorlatinib. After a 2-week interruption, lorlatinib was resumed at a reduced dose with satisfactory glycemic control. This case highlights the importance of vigilant glucose monitoring for patients receiving lorlatinib, especially those with preexisting diabetes, to prevent life-threatening complications such as DKA.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Alecensa (alectinib) • Lorbrena (lorlatinib)
1m
Safety and Efficacy of Lorbrena (clinicaltrials.gov)
P=N/A, N=683, Recruiting, Pfizer | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2025 --> Apr 2026
Trial completion date • Trial primary completion date
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Lorbrena (lorlatinib)
1m
Spectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid. (PubMed, Endocr Relat Cancer)
FDA-approved NTRK inhibitors entrectinib and larotrectinib effectively blocked TG::NTRK1 signaling in vitro and inhibited xenograft tumor growth in vivo. In summary, we report a spectrum of TG gene fusions as recurrent oncogenic events in thyroid cancer and NIFTP that drive strong overexpression of partner genes, frequently RTKs. The TG::NTRK1 fusion is prone to dimerization, activates oncogenic signaling, drives tumorigenesis in thyroid cells, and, like other fusions involving RTKs, represents a potential therapeutic target in thyroid cancer.
Journal
|
ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR1 (Fibroblast growth factor receptor 1) • IGF2 (Insulin-like growth factor 2) • IGF2BP1 (Insulin Like Growth Factor 2 MRNA Binding Protein 1) • NTRK (Neurotrophic receptor tyrosine kinase) • TG (Thyroglobulin)
|
BRAF V600E • BRAF V600 • ALK positive
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
1m
New trial
|
zidesamtinib (NVL-520)
1m
Lorlatinib Induced Blindness: A Rare Entity. (PubMed, Pract Radiat Oncol)
While ocular side effects such as photopsia, blurred vision, vitreous floaters and diplopia have been documented with another ALK TKI, crizotinib, there are few reports of such effects with lorlatinib [3]. Herein we present a case of bilateral optic neuropathy, initially misdiagnosed as optic nerve metastases and treated with palliative radiotherapy.
Journal
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ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Xalkori (crizotinib) • Lorbrena (lorlatinib)
2ms
Rare dual MYH9-ROS1 fusion variants in a patient with lung adenocarcinoma: A case report. (PubMed, Medicine (Baltimore))
We must pay attention to rare dual short and long variants of the MYH9-ROS1 fusions, it may affect the efficacy of ROS1-tyrosine kinase inhibitors targeted therapy.
Journal
|
TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MYH9 (Myosin Heavy Chain 9)
|
TP53 mutation • ROS1 fusion
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Xalkori (crizotinib) • Lorbrena (lorlatinib)
2ms
A rationale for the poor response to alectinib in a patient with adenocarcinoma of the lung harbouring a STRN-ALK fusion by artificial intelligence and molecular modelling: a case report. (PubMed, Transl Lung Cancer Res)
Our model calculations suggested that the effect of the translocation was to induce the dimerization of ALK into a complex that distorted the binding pocket, which is the same for alectinib, lorlatinib and crizotinib. Our observations suggest that molecular modelling based on artificial intelligence (AI) tools may offer potential predictive information in fusions with rare partner genes. Further retrospective and prospective studies are warranted to demonstrate the predictive robustness of these tools.
Journal
|
ALK (Anaplastic lymphoma kinase) • STRN (Striatin)
|
ALK fusion • ALK translocation
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)
2ms
Efficacy and safety of Iruplinalkib in real-world patients with ALK-positive and ROS1-positive NSCLC (ChiCTR2400092150)
P=N/A, N=80, Recruiting, Second Hospital of Shanxi Medical University; Second Hospital of Shanxi Medical University
New trial
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK positive • ROS1 positive
|
Qi Xinke (iruplinalkib)
2ms
New P4 trial
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Lorbrena (lorlatinib)
2ms
Multicenter Real-World Cohort Study of Lorlatinib for Treatment-Related Hyperlipidemia (ChiCTR2400092915)
P4, N=167, Peking University Third Hospital; Peking University Third Hospital
New P4 trial
|
IL6 (Interleukin 6) • CRP (C-reactive protein)
|
Lorbrena (lorlatinib)
2ms
Trial initiation date
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
Augtyro (repotrectinib)
2ms
EML4-ALK-Positive Ovarian Cancer With Intracranial Metastasis Responds to Lorlatinib: A Case Report and Literature Review. (PubMed, Clin Case Rep)
We report a case showing that lorlatinib is effective in treating EML4-ALK-positive low-grade serous ovarian cancer (LGSO) with intracranial metastasis. This may be the first clinical evidence of LGSO benefit from ALK inhibitors, to provide evidence for the use of ALK inhibitors in more ovarian cancer patients with EML4-ALK fusion and promoting new ideas for the study of EML4-ALK targets in ovarian cancer.
Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK positive • EML4-ALK fusion • ALK fusion
|
Lorbrena (lorlatinib)
2ms
STARTRK-2: Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) (clinicaltrials.gov)
P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
|
ALK rearrangement • ROS1 rearrangement
|
Xalkori (crizotinib) • Rozlytrek (entrectinib)
2ms
Population pharmacokinetics of iruplinalkib in healthy volunteers and patients with solid tumors. (PubMed, Clin Transl Sci)
Iruplinalkib (WX-0593), a selective oral ALK/ROS1 tyrosine kinase inhibitor, was approved in China as first-line therapy for ALK-positive non-small-cell lung cancer (NSCLC) and for the treatment of locally advanced or metastatic ALK-positive NSCLC that has progressed following crizotinib therapy. No covariate had a clinically meaningful impact on iruplinalkib exposure. These results indicate that dose adjustment of iruplinalkib is not necessary, based on the aforementioned covariates, for ALK-positive NSCLC patients.
PK/PD data • Journal
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK positive
|
Xalkori (crizotinib) • Qi Xinke (iruplinalkib)
2ms
Newly emerged ROS1 rearrangement in a patient with lung adenocarcinoma following resistance to immune checkpoint inhibitors: a case report. (PubMed, Front Oncol)
We reported a case of lung adenocarcinoma without driver alteration that developed resistance to pembrolizumab and newly emerged CD74-ROS1 fusion, and achieved a partial response after entrectinib treatment. We propose that new therapeutic targets may emerge for this patient population following long-term immunotherapy. Thus, we advocate for regular monitoring of tumor genetic status, which could yield unexpected benefits.
Journal • Checkpoint inhibition
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD74 (CD74 Molecule) • IR (Insulin receptor)
|
ROS1 fusion • ROS1 rearrangement
|
Keytruda (pembrolizumab) • Rozlytrek (entrectinib)
2ms
Case report: Therapeutic response to lorlatinib in advanced large-cell neuroendocrine carcinoma of the lung and breast cancer: a heterochronous double malignancy perspective. (PubMed, Front Pharmacol)
The treatment has been continued for over 25 months since the initiation of ALK Tyrosine kinase inhibitor (ALK-TKI) therapy. This case suggested that ALK-positive advanced LCNEC patients might benefit from first-line intervention with lorlatinib, particularly for managing brain metastases.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion • ALK mutation
|
Lorbrena (lorlatinib)
3ms
PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease. (PubMed, Clin Lung Cancer)
The PEARL study (CTONG2303) will evaluate efficacy of lorlatinib in CNS metastases in ALK+ NSCLC using refined CNS response evaluation criteria, with biomarker analyses providing insights into response and resistance mechanisms.
P2 data • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Lorbrena (lorlatinib)
3ms
Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer. (PubMed, Cell Death Dis)
Here, we investigate the kinase responses in EML4-ALK V1 and V3-harbouring NSCLC cancer cells after acute inhibition with ALK TKI, lorlatinib (LOR)...We found that EML4-ALK cells made resistant to LOR are sensitive to inhibition of ERBB and AKT. These findings emphasize the important roles of AKT and ERBB3 to regulate signalling after acute LOR treatment, identifying them as potential targets that may be beneficial to prevent adaptive resistance to EML4-ALK-targeted therapies in NSCLC.
Journal
|
EML4 (EMAP Like 4) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
|
ALK positive • ALK fusion
|
Lorbrena (lorlatinib)