Ensacove (ensartinib) / Betta Pharma - LARVOL DELTA

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Efficacy and Safety of Ensartinib as Adjuvant Therapy in Stage I ALK-positive NSCLC Patients With High Risk Factors [WITHDRAWN] (ESMO Asia 2025) - No abstract available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

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

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

Preclinical Prediction of Resistance Mutations and Proposal of Sequential Treatment Strategies for ALK-positive Lung Cancer Using Next-generation ALK Inhibitors. (PubMed, Pharm Res) - "• A PCR-based mutation prediction system was successfully applied to fourth-generation ALK inhibitors. • Neladalkib showed efficacy against G1202R-positive relapses with minimal evidence of secondary resistance mutations. • Sequential combinations of gilteritinib with either neladalkib or ensartinib may sustain efficacy and delay resistance in I1171N-positive relapses."

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

Ensartinib Exhibits Potential Synergistic Effects With Radiotherapy in ALK-Positive Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "A total of 97 NSCLC patients with baseline brain metastases who were ALK-positive and crizotinib-resistant received ensartinib treatment. Furthermore, in-vitro experiments demonstrated that ensartinib combined with radiotherapy at various doses exhibited significantly enhanced inhibition of cell proliferation (P < 0.0001). Conclusions : Both in-vitro experiment and clinical study data demonstrate that the combination of ensartinib and radiotherapy exhibits a potential synergistic effect."

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

Neoadjuvant Ensartinib for ALK-Positive (ALK+) Non-Small Cell Lung Cancer (NSCLC): A Multicenter, Real-World Study (IASLC-WCLC 2025) - "No patients had grade ≥ 3 treatment-related AEs. Conclusions : Neoadjuvant ensartinib demonstrated a promising antitumor activity in ALK + NSCLC with high rates of MPR, pCR, and ORR, along with acceptable tolerability."

Clinical • Real-world • Real-world evidence • Dermatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pruritus • Solid Tumor • ALK

Comparative Analysis of Circulating Tumor DNA Monitoring Strategies in Advanced NSCLC With MET Exon 14 Skipping Treated With Ensartinib (IASLC-WCLC 2025) - "METex14 ctDNA clearance offers the highest specificity for treatment response, while broader mutation panels improve sensitivity for molecular progression. Our findings support the integration of early and longitudinal ctDNA dynamics into personalized monitoring and therapeutic decision-making for MET-targeted therapy."

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

LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib. (PubMed, J Pharm Biomed Anal) - "After the validation, 74 plasma samples were measured in the application phase and all results but one fell within the validated ranges. This assay allows simultaneous quantification of nine novel targeted therapies and supports therapeutic drug monitoring."

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

China-based Betta Pharmaceuticals…announced that China’s…NMPA has approved its clinical‑trial application for the bispecific antibody MCLA‑129 in combination with the multi‑targeted kinase inhibitor ensartinib to treat patients with advanced solid tumors exhibiting MET amplification or overexpression (flcube.com) - "Phase I/II trials will commence in Q4 2025 to evaluate safety, tolerability, and preliminary efficacy."

New P1/2 trial • Solid Tumor

X-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Fudan University | Unknown status ➔ Active, not recruiting | Trial completion date: Oct 2020 ➔ Jun 2026 | Trial primary completion date: Jul 2020 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Organizing pneumonia in ALK+ non-small cell lung cancer treated with ceritinib: a case report. (PubMed, Discov Oncol) - "OP should be considered when new lesions appear in the lungs of lung cancer patients, and distinguished from infectious pneumonia, metastasis, or cancer progression. In this respect, pathological biopsy plays an important role in diagnosis. In our case, discontinuation of ceritinib and regular steroid administration were effective."

Journal • Cough • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ALK

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 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Biomarker • Trial completion date • Trial primary 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

Amylase-producing lung adenocarcinoma with an anaplastic lymphoma kinase fusion mutation: a case report. (PubMed, Lab Med) - "We suggest that serum amylase may be a tumor marker that may lead to a more effective approach to the diagnosis and treatment of related diseases."

Journal • Gastroenterology • Gastrointestinal Disorder • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Shifting landscape of resistance to next-generation ALK inhibitors with evolving treatment paradigm in ALK+ lung cancer. (ASCO 2025) - "Funded by No funding sources reported Background: Next-generation (gen) ALK tyrosine kinase inhibitors (TKIs) are standard first-line (1L) therapy for patients (pts) with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (mNSCLC), having supplanted crizotinib (criz)... This retrospective study included pts with ALK+ mNSCLC who received 2G ALK TKIs (alectinib, brigatinib, ceritinib, ensartinib) or 3G TKI lorlatinib (lorl) and had post-progression tissue (TBx) or liquid bx (LBx) assessed by next-generation sequencing (NGS)... In this largest analysis of post-2G/3G ALK TKI TBx/LBx to date, on-target resistance was less freq after 2G/3G TKIs in pts treated with the current paradigm (upfront 2G/3G ALK TKIs) than the past approach (2G/3G TKI after 1L criz). These findings crystallize a shifting resistance landscape and indicate an increasing role for off-target resistance with upfront 2G/3G TKIs, highlighting a need to uncover and therapeutically address off-target..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • MET

Ensartinib as postoperative adjuvant therapy in patients with ALK-positive non-small cell lung cancer (NSCLC): A registered, retrospective, real-world study. (ASCO 2025) - "To our knowledge, this real-world study has the largest sample size on postoperative adjuvant therapy with ALK inhibitors. In this real-world setting, ensartinib demonstrated encouraging efficacy and well-tolerated safety profile among stage IA1-IIIB ALK-positive NSCLC, providing a potential adjuvant therapy option in this patient population."

Real-world • Real-world evidence • Retrospective data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Ensartinib in a primary pulmonary ALK-rearranged mesenchymal neoplasm harboring a novel HMBOX1::ALK fusion: a case report and literature review. (PubMed, Front Med (Lausanne)) - "The family of ALK-rearranged mesenchymal neoplasms is expanding and ensartinib could be a potential treatment option for patients with HMBOX1::ALK. Repeated biopsy and NGS detection are critical to guide treatment selection at disease progression."

Journal • Oncology • ALK • HMBOX1 • NF2