Alecensa (alectinib) / Roche - LARVOL DELTA

Chemometrically assisted optimization and validation of the HPLC method for the analysis of alectinib and its related impurity with measurement uncertainty evaluation and whiteness, blueness, and greenness profile assessments. (PubMed, BMC Chem) - "Also, the whiteness of the method was calculated with the newly developed White Analytical Chemistry tool. The method can be used to assay alectinib and its impurity agents in its formulation in quality control laboratories."

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

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

Shifting landscape of resistance to next-generation ALK inhibitors with evolving treatment paradigm in ALK+ lung cancer. (ASCO 2025) - "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 resistance."

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

The prognostic impact of TP53 mutation on survival outcomes in ALK fusion–positive lung cancer. (ASCO 2025) - "Crizotinib was the most commonly used ALKi (58.1%, n=50), while ceritinib, alectinib, and lorlatinib were used in 9.3% (n=8), 17.4% (n=15), and 15.1% (n=13) patients respectively. TP53 co-mutation has a negative prognostic impact in patients with ALK rearranged lung cancer. Studies evaluating fourth generation ALKi, or the addition of chemotherapy in these patients are warranted."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • TP53

Resistance to Anti EGFR Through the Successive and Cumulative Acquisition of Two New Oncogenic Addictions: BRAF and ALK (ATS 2025) - "She received Gefitinib on the first line...Following progression on chemotherapy, the patient receives targeted therapies combining Dabrafenib, Trametinib and Osimertinib. Due to a dissociated response after 4 months of treatment, a 5th line of Paclitaxel Bevacizumab was initiated. Following a new progression and the presence of an ALK rearrangement on the re-biopsy, treatment with Alectinib was then proposed. The response was dissociated and a final line was therefore proposed before stopping active treatments for toxicity and deterioration in general condition. This case reports a resistance to anti-EGFR by the successive and cumulative acquisition of two new oncogene addictions and emphasizes the importance of rebiopsy at each progression on targeted therapy if feasible."

CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor • ALK • BRAF

Real-world treatment patterns and time-to-treatment discontinuation among advanced ALK-positive non-small cell lung cancer patients. (ASCO 2025) - " Among 680 patients, 1L therapy distribution was as follows: crizotinib (n=366, 53.8%), alectinib (n=267, 39.3%), brigatinib (n=22, 3.2%), and ceritinib (n=25, 3.7%). This study provides real-world evidence on TTD and treatment patterns among advanced ALK+ NSCLC patients. Transition rates to 2L ALK TKIs were lower than expected based on clinical trials, with high rates of discontinuation without transition. With alectinib, brigatinib, and lorlatinib equally recommended as 1L options in US clinical guidelines, these findings provide real-world evidence to help clinicians differentiate among therapies and guide treatment sequencing decisions."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Real-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors. (PubMed, Clin Lung Cancer) - "AKI/CKD events were frequent post-ALKi initiation (using creatinine-based eGFR), with a minority resulting in treatment change. Mean eGFR declined in the 90-days post-ALKi start. Most patients had mild CKD, with eGFR recovering postdrug cessation. AKI did not impact OS. Our findings suggest that most patients may continue ALKi therapy despite creatinine-based eGFR changes."

Journal • Real-world evidence • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Hypertension • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • ALK • CST3

Lorlatinib therapy in relapsed/refractory ALK+ lymphomas previously treated with tyrosine kinase inhibitors. (ASCO 2025) - "Clinical Trial Registration Number: EudraCT2016-003970-41 Background: ALK+ Lymphomas are aggressive diseases with poor prognosis when chemoimmunotherapy (CIT) and Crizotinib fail...2 pts also received other TKIs (Alectinib and Ceritinib)... Our analysis confirms Lorlatinib's efficacy and safety as salvage therapy. Achieving a CR at M1 was found to be the most important prognostic factor for survival. Adverse events are manageable with dose adjustments."

IO biomarker • Alzheimer's Disease • B Cell Lymphoma • CNS Disorders • Dyslipidemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • ALK • CLTC • EML4

SPRING: Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Peking University Shenzhen Hospital

Biomarker • New P2 trial • Oncology

Neoadjuvant and adjuvant iruplinalkib in resectable ALK or ROS1 fusion-positive, non-small cell lung cancer (NSCLC): The preliminary results of the single-arm, exploratory Neo-INFINITY study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05765877 Background: The ALNEO, NAUTIKA1, and SAKULA studies found perioperative alectinib and ceritinib were effective for resectable ALK-positive NSCLC. Neoadjuvant iruplinalkib is effective and feasible for resectable ALK- or ROS1-positive NSCLC, with acceptable safety profiles. Stage 2 of the study is ongoing, and long-term results are awaited. Efficacy endpoints.Note: Data are presented as n (%)."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • ROS1

CUPISCO: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site (clinicaltrials.gov) - P2 | N=528 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024

Trial completion • Trial completion date • Oncology

Treatment of metastatic ALK-positive non-small cell lung cancer: indirect comparison of different ALK inhibitors using reconstructed patient data. (PubMed, Front Oncol) - "Second- and third-generation ALKi, including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib, have shown better efficacy than crizotinib. In this indirect comparison using reconstructed patient data, lorlatinib emerged as the most effective ALKi, showed the most favorable HR for PFS compared to the other ALKi, although it did not reach statistical significance versus alectinib and ensartinib. Additionally, lorlatinib showed the highest efficacy in the control of CNS progression."

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

Beyond Risk Factors: A Young Non-smoker's Battle With Metastatic Lung Cancer (ATS 2025) - "Molecular testing revealed an ALK fusion, leading to the initiation of alectinib, an effective targeted therapy for ALK-positive NSCLC...Future research should focus on identifying genetic alterations associated with early-onset, advanced NSCLC to improve understanding and management. Early diagnosis and targeted therapies can significantly improve outcomes, emphasizing the importance of clinician awareness."

Clinical • Metastases • Cardiovascular • Endocrine Disorders • Endometriosis • Gynecology • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Women's Health • ALK • NKX2-1

Caught in the Lung Crossfire: Fatal Case of Lorlatinib-induced Pneumonitis and ARDS in a Patient With ALK-positive NSCLC (ATS 2025) - "Lorlatinib-induced pneumonitis is infrequently reported, but early recognition is crucial as it can progress to life-threatening respiratory failure.Case Description: We present a case of a 63-year-old non-smoker man who was initially diagnosed with stage IIIA NSCLC, underwent left upper lobectomy, followed by adjuvant chemotherapy with four cycles of Alimta and Cisplatin, followed by adjuvant Alectinib. Early drug discontinuation and corticosteroid therapy are critical, but even with aggressive management, outcomes may be poor. This case highlights the need for further research into the pathophysiology and risk factors associated with TKI-induced pneumonitis to improve outcomes and guide future therapy."

Clinical • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • ALK

Beyond the Lung: A Case of Alectinib-Induced Hypertriglyceridemia Pancreatitis (ATS 2025) - "However, a severe case leading to respiratory failure has been reported. Despite documented increases in amylase levels in clinical trials, pancreatitis is often overlooked as a potential side effect of ALK inhibitors due to its infrequent reporting."

Clinical • Anemia • Dyslipidemia • Hematological Disorders • Hepatology • Hypertriglyceridemia • Immunology • Liver Failure • Lung Adenocarcinoma • Lung Cancer • Myositis • Non Small Cell Lung Cancer • Oncology • Pain • Pancreatitis • Respiratory Diseases • Solid Tumor • ALK

ECMO in a Stage IV Lung Cancer Patient: A Case for Expanding Indications in the Era of Cancer Remission (ATS 2025) - "However, as cancer treatments improve and patients with advanced disease achieve remission, the need to reevaluate these institutional policies should be explored.This case illustrates the successful use of ECMO in a patient with stage 4 lung cancer who presented with ARDS.Case Presentation: A 54-year-old male with a history of stage 4 lung cancer with brain metastasis, currently in remission after three years of treatment with Alectinib, was admitted with a vasovagal syncopal episode, and headache, however on day three of admission he was diagnosed with hospital-acquired pneumonia...As oncology continues to evolve, with many patients achieving prolonged remissions in the era of rapidly changing cancer treatments, critical care protocols should adapt to consider the potential benefits of ECMO in patients with metastatic cancer. This case advocates for a broader application of ECMO and challenges the current contraindications to not consider in advance cancer patients."

Clinical • Metastases • Acute Respiratory Distress Syndrome • Infectious Disease • Lung Cancer • Oncology • Pain • Pneumonia • Respiratory Diseases • Solid Tumor

Do Utility Scores Derived From Different Preference-Based Measurements Influence the Results of Cost-Effectiveness Analysis? (ISPOR 2025) - "The model B was built to compare sintilimab with camrelizumab as 1 st -line therapy. The model C was built to compare anlotinib with support care as 3 rd -line therapy... In model A, when utilities were measured by Q-5D-5L, compared with chemotherapy, alectinib provided 1.91 additional QALYs (10.08 QALYs vs. 8.18 QALYs)... The utilities measured by EQ-5D-5L were higher than those measured by SF-6Dv2, and the utilities measured by SF-6Dv2 were more clustered across different health states. Compared to using the utilities measured by SF-6Dv2, using EQ-5D-5L results in a higher QALY and larger incremental QALY. This difference would further expand as the patient’s survival time increases."

Cost effectiveness • HEOR • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Real-world adoption of adjuvant molecularly targeted therapy and immunotherapy for resected stage Ib-III non-small cell lung cancer within the Veterans Health Administration. (ASCO 2025) - "Adjuvant therapies, including platinum-based chemotherapy (cisplatin and/or carboplatin), molecularly targeted therapies (osimertinib or alectinib), and immunotherapies (durvalumab, atezolizumab, pembrolizumab, or nivolumab), given within 6 months after surgery were assessed. While the overall rate of adjuvant systemic therapies for resected stage Ib-III NSCLC has remained stable in recent years, there has been a notable increase in the adoption of molecularly targeted therapies and immunotherapies into clinical practice. Further research is needed to examine patient selection using appropriate genomic and biomarker testing and to ensure that these emerging therapies are offered to patients with resected early-stage NSCLC who meet selected guideline- or clinical pathway-based criteria in the adjuvant setting. Frequencies of adjuvant systemic therapies."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Treatment strategies and outcomes of inflammatory myofibroblastic sarcoma: Insights from a retrospective single-center study. (ASCO 2025) - "This patient with the CLTC-ALK fusion progressed on crizotinib therapy but has had a partial response to 2nd generation ALK inhibitor, alectinib. EIMS is an aggressive variant of IMT with a paucity of cases reported in the literature. This single institution retrospective review displayed that EIMS was more likely to recur and/or present with metastatic disease compared to IMT, with the first known report of a CLTC-ALK fusion in EIMS which usually harbors RANBP2-ALK fusions. A multi-institutional study will be helpful to understand the full slate of prognostic factors and biology to tailor the best treatment regimen for this biologically distinct sarcoma."

Retrospective data • Bladder Cancer • Oncology • Pediatrics • Sarcoma • Solid Tumor • CLTC • RANBP2

Are patients with early-stage non-small cell lung cancer receiving timely testing for the ALK rearrangement? (ASCO 2025) - "This study showed that ALK testing among eNSCLC patients has increased following FDA approval of adj. alectinib. For many patients systemic therapy is initiated before knowledge of ALK status; such care is sub-optimal because ALK+ is associated with a lack of benefit from immunotherapy."

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

Assessing the efficacy of ALK inhibitors in ALK-positive non-small cell lung cancer: A real-world data analysis. (ASCO 2025) - "Alectinib and crizotinib were the most commonly used ALK inhibitors, administered to 41.7% and 58.3% patients, respectively. This study represents the largest dataset from Russia on the treatment of ALK-positive lung cancer patients with ALK inhibitors, confirming findings similar to the international ALEX study. Our results reinforce the efficacy of ALK inhibitors in a real-world setting and suggest that future generations of these agents could provide even greater benefits. The consistency between these findings and those of controlled trials underscores the potential of ALK inhibitors in improving clinical outcomes for this patient population."

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

Advancing targeted therapies in oncology: The role of alectinib in managing ALK-positive non-small cell lung cancer. (ASCO 2025) - "Alectinib has emerged as a highly effective treatment option for patients with ALK-positive NSCLC, offering distinct advantages over traditional chemotherapies. Its ability to limit CNS metastases, coupled with its manageable side-effect profile, positions it as a leading therapy in this field. As the clinical landscape for ALK-positive NSCLC evolves, it is vital for oncologists, surgeons, and healthcare teams to stay informed about alectinib's evolving role in neoadjuvant treatment protocols."

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

Alectinib in children and adolescents with solid or CNS tumors harboring ALK-fusions: A data update from the iMATRIX alectinib phase I/II open-label, multi-center study. (ASCO 2025) - P1/2 | "Alectinib continues to have a favourable safety profile in pediatric patients. Despite this being a very challenging population to treat, clinical efficacy results are transformational with the majority of patients experiencing a tumor response."

Clinical • P1/2 data • Astrocytoma • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioma • Hematological Malignancies • Infectious Disease • Lymphoma • Malignant Glioma • Melanoma • Mesothelioma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Pleomorphic Xanthoastrocytoma • Renal Cell Carcinoma • Solid Tumor • Wilms Tumor • ALK • CDC42BPB • CLIP1 • CLTC • DCTN1 • EML4 • KIF5B • KIF5C • RANBP2 • STRN • TPM3 • ZEB2

Delayed or upfront brain radiotherapy in treatment-naïve lung cancer patients with asymptomatic or minimally symptomatic brain metastases and ALK rearrangements (DURABLE). (ASCO 2025) - P1/2 | "Alectinib was shown to be superior to crizotinib in the first-line treatment of patients with ALK-positive NSCLC in the ALEX trial, and the intracranial response rate (CNS ORR) was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not. Secondary endpoint will be intracranial progression free survival at 12 months (icPFS12), response rate and icPFS, OS, and safety and tolerability. The study is open and accruing at 4 sites."

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

Efficacy and safety of alectinib in pediatric and adult patients with ALK altered advanced solid tumors: Results from the TACKLE phase II trial, a MASTER KEY substudy (NCCH1712/MK003). (ASCO 2025) - P2 | "Our study showed that patients with ALK alterations treated with alectinib achieved sustained clinical benefit, meaningful survival outcomes, and safety consistent with previous data. Greatest benefit was observed for the ALK fusion population including pediatric patients. These data support the potential role of alectinib as a tumor-agnostic therapy for both pediatric and adult patients with ALK altered solid tumors."

Clinical • Metastases • P2 data • Embryonal Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pediatrics • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ALK