Ensacove (ensartinib) / Betta Pharma - LARVOL DELTA

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=1376 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Jan 2027

Biomarker • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • BRAF

Exploratory clinical study on preserving organs in patients with stage II-III non-small cell lung cancer(The Future Star) (ChiCTR) - P4 | N=598 | Recruiting | Sponsor: Jiangsu Cancer Hospital; Jiangsu Cancer Hospital

New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

EFFICACY AND SAFETY OF ENSARTINIB-BASED REGIMENS IN ALK-POSITIVE LYMPHOMA: A REAL-WORLD RETROSPECTIVE STUDY (EBMT 2026) - "Among all patients, 22.2% received ensartinib alone, 22.2% received ensartinib plus R-CHOP regimen, and 55.6% received ensartinib plus other chemotherapy regimens. Ensartinib-based regimens demonstrated promising preliminary efficacy and manageable toxicity in patients with R/R ALK+ lymphoma, warranting further prospective validation."

Real-world • Real-world evidence • Retrospective data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Solid Tumor • ALK

Ensartinib as adjuvant therapy in patients (pts) with stage IB–IIIB ALK-positive (ALK+) non-small cell lung cancer (NSCLC) after complete tumor resection: The phase III randomized ELEVATE trial (ESMO 2025) - P3 | "Conclusions Adjuvant ensartinib is the first ALK inhibitor to show a statistically significant and clinically meaningful improvement in DFS in pts with stage IB-IIIB (T3N2M0) ALK-positive NSCLC after complete tumor resection and adjuvant chemotherapy. Adjuvant ensartinib provides an effective new treatment strategy for these pts."

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK

Comparative analysis of ctDNA monitoring strategies in advanced NSCLC with MET exon 14 skipping mutations treated with ensartinib. (PubMed, NPJ Precis Oncol) - "Among the three paradigms, MET-specific monitoring provided the most favorable diagnostic performance to identify long-term responders, with a specificity of 90% and a positive predictive value of 80%. These data demonstrate that early MET-specific ctDNA clearance is a robust on-treatment biomarker for ensartinib benefit in METex14 NSCLC, while broader ctDNA profiling remains valuable for uncovering emerging resistance mechanisms."

Circulating tumor DNA • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Treating Patients With Melanoma and ALK Alterations With Ensartinib (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • ALK • BRAF

Cost of managing brain metastases in ALK-positive advanced NSCLC patients receiving first-line ALK TKIs in China. (PubMed, Lung Cancer Manag) - "Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients."

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

Comparison of the efficacy based on clinicopathological characteristics and the safety of first-line treatments for patients with advanced ALK rearrangement non-small cell lung cancer: a network meta-analysis. (PubMed, Front Oncol) - "Specifically, lorlatinib demonstrated superior efficacy in the Non-Asian subgroup (86.8%), patients without brain metastasis (84.7%), those with Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1 (78.5%), males (71.2%), females (83.9%), patients aged < 65 years (74.3%), and never-smoking patients (89.7%)...Ensartinib achieved the optimal PFS in the Asian subgroup (71.8%)...Alectinib had the lowest hepatic and gastrointestinal AEs risk, while iruplinalkib had the lowest hematological AEs risk. https://www.crd.york.ac.uk/prospero/, identifier CRD42023495527."

Journal • Retrospective data • Review • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A Multicenter, Randomized Controlled Study to Assess the Effects of Ensartinib Versus Placebo Following Chemoradiation in ALK Positive Patients With Stage III Unresectable Non-small Cell Lung Cancer (ChiCTR) - P2 | N=45 | Not yet recruiting | Sponsor: Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A randomized controlled clinical study on postoperative adjuvant targeted therapy and MRD observation for stage IA non-small cell lung cancer (ChiCTR) - P4 | N=178 | Not yet recruiting | Sponsor: Beijing chest hospital capital medical university; Beijing Chest Hospital Capital Medical University

New P4 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A single-arm, multicenter clinical study of ensartinib combined with chemotherapy as neoadjuvant therapy for ALK-positive non-small cell lung cancer (NSCLC) (TD-ENSEMBLE study) (ChiCTR) - P4 | N=20 | Not yet recruiting | Sponsor: The Second Affiliated Hospital of Air Force Medical University; The Second Affiliated Hospital of Air Force Medical University

New P4 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "Ensartinib represents a new first-line option for patients with ALK-positive NSCLC. ClinicalTrials.gov Identifier: NCT02767804."

Clinical • Journal • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

TD-ENSEMBLE: Neoadjuvant Therapy With Ensartinib Combined With Chemotherapy for ALK-positive Non - Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=20 | Not yet recruiting | Sponsor: Tang-Du Hospital

New P1/2 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Pulmonary nodules with explosive calcification were finally diagnosed as lung adenocarcinom: A case report. (PubMed, Medicine (Baltimore)) - "This case emphasizes that nodules with diffuse, popcorn-like calcification do not rule out the possibility of lung cancer. A comprehensive evaluation integrating multidimensional imaging features is necessary. For nodules with conflicting imaging characteristics, minimally invasive surgical resection remains valuable for diagnosis. This approach broadens our diagnostic perspective on calcified nodules, enhances clinicians' understanding of lung adenocarcinoma, and reduces the rate of misdiagnosis."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • ALK

The Efficacy and Safety of Ensartinib as Adjuvant Therapy in Stage I ALK-positive NSCLC Patients With High Risk Factors [WITHDRAWN] (ESMO Asia 2025) - No abstract available

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Ensartinib After Chemoradiotherapy in Stage III ALK-Mutated NSCLC (clinicaltrials.gov) - P2 | N=45 | Not yet recruiting | Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development and validation of a quick and sensitive UPLC-MS/MS method for measuring ensartinib in HLMs: investigation of structural alerts associated with metabolic lability and in silico toxicity. (PubMed, Analyst) - "EST and Encorafenib (ECB as the internal standard) were differentiated using an isocratic mobile phase system on a reversed stationary phase (Eclipse Plus C18) column. In silico data proposed that minor structural modifications to the dichlorophenyl moiety or the piperazine ring during drug design may enhance the safety profile and metabolic stability relative to the properties of EST. Evaluating the EST metabolic stability and in silico ADME characteristics is essential for advancing innovative therapeutic research focused on improving metabolic stability."

Journal • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • ALK • AXL • MET • ROS1

Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes. (PubMed, JTO Clin Res Rep) - "This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21). For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI."

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

Treatment process of ALK and ROS1 double-rearranged lung adenocarcinoma cell carcinoma: a case report. (PubMed, AME Case Rep) - "The patient received first-line chemotherapy with pemetrexed (820 mg on day 1) plus cisplatin (40 mg on days 1-3) every 21 days and achieved a remarkable progression-free survival (PFS) of 48 months...She was subsequently treated with ensartinib (225 mg once daily), yielding a favorable response...Unless there are studies with large cohorts clarifying the case, an individualized regimen-potentially starting with chemotherapy and transitioning to targeted agents-may be justified. Further clinical experience and collaborative research are essential to develop evidence-based guidelines for this exceptionally rare subset."

Journal • Cough • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK • EML4 • ROS1

Patient-derived organoid facilitating personalized medicine in non-small cell lung cancer: two case reports. (PubMed, Front Oncol) - "The corresponding PDO model demonstrated sensitivity to a combination of pemetrexed, carboplatin, and osimertinib, but insensitivity to osimertinib monotherapy...The patient had progressed on multiple lines of therapy, including alectinib and lorlatinib. The PDO model showed sensitivity to brigatinib but insensitivity to ensartinib. Subsequent treatment with brigatinib induced a PR that was sustained for 5.8 months; the patient survived for a total of 9 months following the initiation of this PDO-guided therapy. These two cases suggests that PDOs derived from primary and metastatic lesions may help optimize treatment regimens for patients with lung cancer brain metastases, thereby enabling personalized therapy and potentially improving survival outcomes."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • EML4 • NRXN1

Efficacy and safety of ensartinib in the treatment of non-small cell lung cancer: A systematic review of clinical trials. (PubMed, J Oncol Pharm Pract) - "Phase III trial confirmed superior PFS with ensartinib compared to crizotinib. This review received no specific funding. The protocol was not registered."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

In a pre-specified interim analysis of the ELEVATE trial, adjuvant ensartinib following chemotherapy resulted in an 80% reduction in the risk of disease recurrence compared with placebo in patients with completely resected, stage IB–IIIB ALK-positive NSCLC. (ESMO.org) - "Disease-free survival (DFS), the primary endpoint, was associated with a hazard ratio (HR) of 0.20 in patients with stage II–IIIB disease (95% confidence interval [CI] 0.11–0.38; p<0.0001) and in the intent-to-treat (ITT) population (95% CI 0.10–0.37; p<0.0001)...Ensartinib also improved the 2-year DFS rate compared with placebo in both populations"

P3 data • Non Small Cell Lung Cancer

Case Report: Treatment response of SQSTM1-ALK fusion lung adenocarcinoma to multiple ALK inhibitors. (PubMed, Front Pharmacol) - "This is the first report of a patient with SQSTM1-ALK fusion who experienced different responses after treatment with alectinib, ensartinib, lorlatinib, and brigatinib. We hope that this case provides clinical evidence to guide treatment strategies for this rare variant and further supports the individualized application of ALK-tyrosine kinase inhibitors (TKIs) in patients with non-classical fusions."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • SQSTM1

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=13 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=98 ➔ 13 | Trial completion date: Oct 2025 ➔ Oct 2026

Biomarker • Enrollment change • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

Severe skin toxicity and early progression following neoadjuvant ensartinib and surgery in anaplastic lymphoma kinase-positive locally advanced lung cancer: a case report. (PubMed, Front Pharmacol) - "After multidisciplinary evaluation and considering the patient's refusal to undergo local therapies, treatment was switched to lorlatinib. The case underscores the need for continued vigilance and individualized surveillance strategies even once favorable pathological responses are achieved. Additionally, the perioperative evolution of skin toxicity highlights the importance of continuous adverse event monitoring and management."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • TP53