^
24d
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)
29d
NRG-LU003: Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025
Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
ALK positive • MET amplification • ALK rearrangement
|
cisplatin • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib) • Ensacove (ensartinib)
2ms
EAGLE: Ensartinib in Combination With Bevacizumab in ALK-positive NSCLC Patients With TP53 Mutation (clinicaltrials.gov)
P2, N=49, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Metastases
|
ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
|
TP53 mutation • ALK positive • ALK mutation
|
Avastin (bevacizumab) • Ensacove (ensartinib)
2ms
New P2 trial
|
Loqtorzi (toripalimab-tpzi) • Ensacove (ensartinib) • Qi Xinke (iruplinalkib) • Semena (befotertinib) • bozitinib (APL-101) • Ariely (adebrelimab) • SHR-A1921
2ms
A novel secondary ALK gene mutation which resistant to second-generation TKIs: a case report and literature review. (PubMed, Front Oncol)
We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib...Ensartinib and ceritinib were administered as second-line and third-line treatments...The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK positive • ALK fusion • ALK mutation • ALK V1180L
|
Alecensa (alectinib) • Zykadia (ceritinib) • Ensacove (ensartinib)
2ms
Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis. (PubMed, Transl Lung Cancer Res)
Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.
Retrospective data • Review • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib) • Ensacove (ensartinib) • Qi Xinke (iruplinalkib) • Anluoqing (envonalkib)
3ms
New P2 trial
|
Mekinist (trametinib) • Xalkori (crizotinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Irene (pyrotinib) • Gavreto (pralsetinib) • Ensacove (ensartinib) • Orpathys (savolitinib) • glecirasib (JAB-21822) • sunvozertinib (DZD9008)
3ms
eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov)
P3, N=290, Active, not recruiting, Xcovery Holdings, Inc. | Trial primary completion date: Jun 2024 --> Dec 2025
Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
Xalkori (crizotinib) • Ensacove (ensartinib)
3ms
Case report: Durable response of ensartinib targeting EML4-ALK fusion in osimertinib-resistant non-small cell lung cancer. (PubMed, Front Pharmacol)
Of note, the clinical response to ensartinib persisted for more than 14 months, superior to the previously reported efficacy of aletinib and crizotinib in osimertinib-failure cases. We reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired EML4-ALK fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the EML4-ALK fusion as a resistance mechanism to osimertinib, ensartinib emerges as a promising treatment option for this specific clinical challenge, offering superior efficacy and good safety.
Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
Xalkori (crizotinib) • Tagrisso (osimertinib) • erlotinib • Ensacove (ensartinib)
4ms
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial) (clinicaltrials.gov)
P2, N=98, Recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Sep 2027
Trial completion date • Trial primary completion date • Metastases
|
Ensacove (ensartinib)
4ms
New P1 trial
|
Ensacove (ensartinib) • itraconazole • rifampicin
5ms
Ensartinib in the treatment of anaplastic lymphoma kinase-positive locally advanced or metastatic patients with lung squamous or adenosquamous carcinoma: A real-world, retrospective study. (PubMed, Asia Pac J Clin Oncol)
Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes.
Retrospective data • Journal • Real-world evidence • Real-world • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
Ensacove (ensartinib)
5ms
Cost-Effectiveness Analysis of 6 Tyrosine Kinase Inhibitors as First-Line Treatment for ALK-Positive NSCLC in China. (PubMed, Clin Med Insights Oncol)
This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)-crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib-as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered.
Journal • HEOR • Cost-effectiveness • Cost effectiveness
|
ALK (Anaplastic lymphoma kinase)
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
6ms
Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP. (PubMed, Cell Biol Toxicol)
Further studies showed rutin can attenuate the hepatotoxicity of ensartinib without antagonizing its antitumor effects. Accordingly, we suggest that TXNIP is the key cause of ensartinib-induced hepatotoxicity and rutin is a potential clinically safe and feasible therapeutic strategy for TXNIP intervention.
Journal
|
TXNIP (Thioredoxin Interacting Protein)
|
Ensacove (ensartinib)
6ms
Two cases of inflammatory myofibroblastic tumor treated with targeted drugs: A case report. (PubMed, Medicine (Baltimore))
Our cases provided some new insights and approaches for the clinical diagnosis and treatment of IMT.
Journal
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STRN (Striatin)
|
Ensacove (ensartinib)
6ms
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Ensacove (ensartinib)
6ms
eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov)
P3, N=290, Active, not recruiting, Xcovery Holdings, Inc. | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Jun 2020 --> Jun 2024
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Ensacove (ensartinib)
7ms
Ensartinib in Combination With Bevacizumab in ALK-positive NSCLC Patients With TP53 Mutation (clinicaltrials.gov)
P2, N=58, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting | Trial primary completion date: Nov 2023 --> Jun 2024
Enrollment open • Trial primary completion date • Combination therapy • Metastases
|
ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
|
TP53 mutation • ALK positive • ALK mutation
|
Avastin (bevacizumab) • Ensacove (ensartinib)
8ms
Chinese expert consensus on iruplinalkib for the treatment of locally advanced or metastatic ALK-positive non-small cell lung cancer (2024 edition) (PubMed, Zhonghua Zhong Liu Za Zhi)
Seven different ALK-TKIs have been approved by the National Medical Products Administration (NMPA) of China, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib. On January 16, 2024, the NMPA approved iruplinalkib for the first-line treatment of locally advanced or metastatic ALK-positive NSCLC patients. In order to better understand the efficacy and safety of iruplinalkib, and facilitate more rationally clinical application of iruplinalkib, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists co-organized experts to compile the "Chinese expert consensus on iruplinalkib for the treatment of locally advanced or metastatic ALK-positive non-small cell lung cancer (2024 edition)".
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib) • Qi Xinke (iruplinalkib)
9ms
Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study. (PubMed, Cancer Commun (Lond))
Ensartinib led to a favorable OS in patients with advanced, crizotinib-resistant, and ALK-positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.
P2 data • Journal • Circulating tumor DNA
|
ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
|
TP53 mutation • ALK positive • ALK mutation
|
Xalkori (crizotinib) • Ensacove (ensartinib)
9ms
Phase classification • Combination therapy
|
Avastin (bevacizumab) • carboplatin • pemetrexed • Ensacove (ensartinib) • Pemfexy (pemetrexed)
9ms
Anaplastic Lymphoma Kinase (ALK) Inhibitors Show Activity in Colorectal Cancer With ALK Rearrangements: Case Series and Literature Review. (PubMed, Oncologist)
Both fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab combined with 5-fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) proved ineffective against the disease...The patient was initially treated with ensartinib monotherapy for 9 months, then with ensartinib combined with local radiotherapy and fruquintinib for another 4 months for isolated hilar hepatic lymph node metastasis. The patient experienced disease progression with an acquired ALK G1202R resistance mutation that responded well to lorlatinib...However, the patient responded remarkably well to alectinib. Our report emphasizes the importance of gene detection in the treatment of malignant tumors, and the significance of ALK mutations in CRC.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK positive • ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK G1202R • CAD-ALK fusion • EML4-ALK G1202R
|
Avastin (bevacizumab) • 5-fluorouracil • Alecensa (alectinib) • Lorbrena (lorlatinib) • oxaliplatin • irinotecan • Ensacove (ensartinib) • Fruzaqla (fruquintinib) • leucovorin calcium
9ms
A Single Dose BE Study of X-396 in Healthy Volunteers Under Fasted Conditions (clinicaltrials.gov)
P1, N=32, Completed, Xcovery Holdings, Inc. | Not yet recruiting --> Completed | Trial completion date: Mar 2023 --> Aug 2023
Trial completion • Trial completion date
|
Ensacove (ensartinib)
9ms
Treating Patients With Melanoma and ALK Alterations With Ensartinib (clinicaltrials.gov)
P2, N=18, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
|
BRAF V600 • ALK fusion • ALK mutation
|
Ensacove (ensartinib)
9ms
China expert recommendations on anaplastic lymphoma kinase-tyrosine kinase inhibitors treatment for advanced non-small cell lung cancer (2024 edition) (PubMed, Zhonghua Yi Xue Za Zhi)
As of June 27, 2023, seven ALK-TKI, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib, have garnered approval from the China National Medical Products Administration (NMPA)(ranking according to the approval time for marketing by NMPA), providing individualized treatment modalities for ALK-positive NSCLC patients. To standardize the application of ALK-TKI, the Chinese Association for Clinical Oncologists and the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care has organized experts to compile the " China expert recommendations on anaplastic lymphoma kinase-tyrosine kinase inhibitors treatment for advanced non-small cell lung cancer (2024 edition)". This treatment expert recommendation provides recommendations in four aspects, encompassing ALK fusion testing, ALK-TKI targeted therapy, ALK-TKI adverse events management, and patient post-treatment follow-up, thus serving as a valuable reference for the standardized treatment of Chinese advanced ALK fusion-positive NSCLC.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib) • Qi Xinke (iruplinalkib)
10ms
A retrospective study of ensartinib-treated ALK-positive locally advanced or metastatic NSCLC patients in China. (PubMed, Lung Cancer Manag)
The most common TRAE was rash (21.1%) and no TRAE led to death. Ensartinib is active and well tolerated for ALK-positive NSCLC patients in real-world clinical settings.
Retrospective data • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Ensacove (ensartinib)
10ms
Comparing efficacy and safety of upfront treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a network meta-analysis. (PubMed, Explor Target Antitumor Ther)
The analysis included 9 RCTs with 2,443 patients receiving eight different treatments: alectinib (at two different dosages), brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Based on the network meta-analysis, alectinib and lorlatinib emerged as the most promising upfront treatment options. These treatments provide prolonged disease control while maintaining an acceptable safety profile.
Retrospective data • Review
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
10ms
Ensartinib is effective in the treatment of advanced non-small-cell lung cancer with MET amplification after multi-line ALK-TKIs resistance: a case report. (PubMed, Anticancer Drugs)
Among these, the MET pathway is one of the signaling pathways that has recently been extensively studied, and activation of this pathway is one of the mechanisms of ALK-independent drug resistance. Here, we report a successful case of an advanced NSCLC patient who was resistant to treatment with ALK TKIs and developed MET amplification, who achieved 23 months of progression-free survival after post-line treatment with ensartinib.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
ALK positive • MET amplification
|
Ensacove (ensartinib)
12ms
Management of Brain Metastases: A Review of Novel Therapies. (PubMed, Semin Neurol)
Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective "rearranged during transfection" inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody-drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene)
|
EGFR exon 20 insertion
|
Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • Retevmo (selpercatinib) • Braftovi (encorafenib) • Alunbrig (brigatinib) • Gavreto (pralsetinib) • Ensacove (ensartinib) • Krazati (adagrasib) • Pozenveo (poziotinib)
12ms
Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Sep 2024
Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
ALK positive • MET amplification • ALK rearrangement
|
cisplatin • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib) • Ensacove (ensartinib) • Pemfexy (pemetrexed)
1year
Adjuvant Therapy of Ensartinib in Stage IB-IIIA ALK-positive Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=80, Recruiting, Hebei Medical University Fourth Hospital | Not yet recruiting --> Recruiting
Enrollment open
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK fusion
|
Ensacove (ensartinib)
1year
Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis. (PubMed, Lung Cancer)
The toxicity spectra of ALK-TKIs differed. Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.
Retrospective data • Review • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK mutation
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
1year
A Bayesian network meta-analysis of ALK inhibitor treatments in patients with ALK-positive non-small cell lung cancer. (PubMed, Cancer Med)
Alectinib was the first choice for patients with ALK-positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long-term follow-up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.
Retrospective data • Journal
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
1year
Prediction of Drug-Drug Interactions with Ensartinib as a Time Dependent CYP3A Inhibitor Using Physiologically Based Pharmacokinetic Model. (PubMed, Drug Metab Dispos)
Therefore, the first ensartinib PBPK model was developed and applied to predict various untested scenarios. The simulation result indicated that the exposure of CYP3A substrate increased significantly and urged the further clinical DDI study.
PK/PD data • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Ensacove (ensartinib)
1year
Ensartinib in Non-small Cell Lung Cancer Patients With Positive ALK (clinicaltrials.gov)
P1, N=48, Completed, Betta Pharmaceuticals Co., Ltd. | Recruiting --> Completed | N=24 --> 48
Trial completion • Enrollment change
|
ALK (Anaplastic lymphoma kinase)
|
Ensacove (ensartinib)
1year
X-396 Capsule in Patients With ALK-positive Non-small Cell Lung Cancer Previously Treated With Crizotinib (clinicaltrials.gov)
P2, N=152, Active, not recruiting, Betta Pharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting
Enrollment closed
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Ensacove (ensartinib)
over1year
Identification of a novel RSRC1-ALK (R6: A20) fusion using next-generation sequencing technique. (PubMed, Cancer Genet)
For the treatment, the patient received ensartinib hydrochloride with a dose of 225 mg per day. He was in a state of progression-free survival for at least 24 months in follow-up with no complications. NGS can be used for exploring treatment options for NSCLC patients with ALK fusion.
Journal • Next-generation sequencing
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement • ALK fusion
|
Ensacove (ensartinib)
over1year
X-396 Capsule in Patients With ALK-positive Non-small Cell Lung Cancer Previously Treated With Crizotinib (clinicaltrials.gov)
P2, N=152, Recruiting, Betta Pharmaceuticals Co., Ltd. | Unknown status --> Recruiting | Trial completion date: Dec 2018 --> Dec 2023
Enrollment open • Trial completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Ensacove (ensartinib)
over1year
Efficacy and safety of ensartinib in ALK-positive non-small cell lung cancer patients with brain metastases: A multicenter, open-label, single-arm, phase II study (ESMO 2023)
Pts received ensartinib as 1st (1/14, 7%) or 2nd (13/14, 93%) -line therapy (with prior crizotinib). Table: 1370P Conclusions Ensartinib showed promising intracranial efficacy with high blood-brain barrier penetration and a tolerable safety profile in ALK+ NSCLC pts with BM. Study is ongoing and final results will be presented in future.
Clinical • P2 data
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Ensacove (ensartinib)
over1year
Mechanisms of Acquired Resistance to ALK Inhibitors Using Plasma Sequencing - Preliminary Data from the ATORG004 Study (IASLC-WCLC 2023)
In Cohort 1 (n=21), 15 (71%) pts had progressed on alectinib, 5 (24%) on ceritinib and 1 (5%) on ensartinib. In Cohort 2 (n=18), pts had progressed on crizotinib followed by alectinib (n=9, 50%), ceritinib (n=4, 22%) or brigatinib (n=3, 17%); 2 (11%) pts progressed on crizotinib, then ceritinib followed by alectinib...Of 5 pts with ALK resistance mutations (I1171N, V1180L, L1196M, G1202R, and E1210K) who subsequently received lorlatinib, repeat ctDNA NGS after 2 months demonstrated clearance of ALK resistance mutation(s) in 4/5 (80%) pts (i.e. undetectable on repeat testing)... Resistance mechanisms to ALK inhibitors are heterogenous, including both ALK dependent and independent pathways. DDR and cell cycle gene alterations were commonly detected and may represent previously unreported acquired resistance alterations. Comprehensive ctDNA NGS analysis at progression may help detect novel resistance alterations in patients on ALK inhibitors.
Preclinical • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KIF5B (Kinesin Family Member 5B) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CDK6 (Cyclin-dependent kinase 6)
|
TP53 mutation • HER-2 amplification • NRAS mutation • HER-2 mutation • MET amplification • ALK rearrangement • FGFR1 amplification • ALK fusion • CDK12 mutation • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • ALK amplification • ALK E1210K • ALK V1180L • EML4-ALK G1202R
|
Guardant360® CDx
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
over1year
Identifying Biomarkers of Response to Ensartinib, Lorlatinib, and Alectinib in an ALK+ Non-Small Cell Lung Cancer Preclinical Model (ResCu) (IASLC-WCLC 2023)
The ResCu system developed two ALKi resistant cell populations from distinct genetic backgrounds under physiologically relevant conditions. Genetic background significantly influenced which ALKi exhibited the most durable response. We identified 124 resistance changes associated with ALKi, 109 of which are unique to one of the three ALKi tested.
Preclinical
|
ALK (Anaplastic lymphoma kinase)
|
Alecensa (alectinib) • Lorbrena (lorlatinib) • Ensacove (ensartinib)
over1year
NEOEAST: A Phase II Study of Ensartinib as Neoadjuvant Therapy for Stage II-IIIB ALK-rearranged Non-small Cell Lung Cancer (IASLC-WCLC 2023)
Secondary endpoints include the pathologic complete response, investigator-assessed objective response rate per RECIST 1.1, disease-free survival, overall survival, and safety as assessed by the incidence of adverse events (CTCAE 5.0). Enrollment began in May 2022 and is ongoing; completion of primary data collection is anticipated in 2024.
Clinical • P2 data
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement • ALK fusion
|
Ensacove (ensartinib)