Alecensa (alectinib) / Roche - LARVOL DELTA

CLINICAL ANALYSIS OF 53 CASES OF RELAPSED OR REFRACTORY CHILDHOOD ALK + ANAPLASTIC LARGE CELL LYMPHOMA (ICML 2025) - "Among the 53 patients, 44 patients were treated with Crizotinib, 33 patients had good response, the ORR rate was 75%, the median time of ALK gene negative conversion was 16 weeks (2–26 weeks), 11 patients without good response to Crizotinib received Alectinib treatment, and 7 patients got good response, the median time of ALK gene negative was 40 weeks (4–56 weeks); 9 patients with central nervous system recurrent received Alectinib alone or in combination with vinblastine, 7 patients had a good response, and the median time to ALK gene negative was 28 weeks(4–44 weeks). ALK inhibitors with or without vinblastine are effective treatment for relapsed and refractory childhood ALCL without serious side effect, allogeneic hematopoietic stem cell transplantation is still the effective treatment for children with ALCL who have a poor response to ALK inhibitors."

Clinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

LORLATINIB THERAPY IN RELAPSED/REFRACTORY ALK + LYMPHOMAS PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS (EHA 2025) - "Background: ALK+ Lymphomas are aggressive diseases with poor prognosis when chemoimmunotherapy (CIT) and Crizotinib fail...Two pts also received other TKIs (Alectinib and Ceritinib).Lorlatinib was administered daily at a dose of 100 mg.The ORR at one month (M1) was 100% (95% CI: 72-100%): 5 CR and 3 PR.Three pts, 2 ALCL [ATIC::ALK], 1 ALCL [NPM::ALK]), underwent Allogeneic Stem Cell Transplant (ASCT) while in CR and resumed Lorlatinib post-transplant... 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

ROLE OF ALK INHIBITORS IN ALK POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA IN ADULTS—EXPERIENCE FROM RUSSIAN NATIONAL RESEARCH CENTER FOR HEMATOLOGY (EHA 2025) - "ALK inhibitors, including crizotinib, alectinib, and ceritinib, have emerged as promising treatments for relapsed/refractory (R/R) ALK+ ALCL, demonstrating high response rates and improved outcomes. This study highlights the efficacy and safety of ALK inhibitors in ALK+ ALCL in adults, both in first-line and relapsed/refractory settings. The addition of ALK inhibitors to first-line therapy for high-risk patients, particularly those with CNS involvement or unfavorable genetic markers, holds significant promise for improving outcomes. Further research is needed to optimize treatment duration, manage resistance mechanisms, and explore combination therapies to maximize the therapeutic potential of ALK inhibitors in ALK+ ALCL"

Clinical • Anemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Protective effects of alectinib on germinal matrix hemorrhage-induced neonatal brain injury. (PubMed, Neuroreport) - "Our data revealed that alectinib reduced oxidative stress, microglia number, and BBB permeability, thereby alleviating secondary brain injury in GMH. Therapies that inhibit ALK signaling may confer neuroprotection against GHM."

Journal • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Oncology • Vascular Neurology • ALK • CLDN5 • IL1B • IL6 • TJP1 • TNFA

CLINICAL EXPERIENCE OF RARE NON-NPM1-ALK MUTATION PROFILES IN PEDIATRIC ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA: A SINGLE-CENTER RETROSPECTIVE STUDY FROM CHINA (EHA 2025) - "ALK inhibitors (crizotinib, alectinib) induced sustained CR in refractory cases. Non-NPM1-ALK mutated ALCL in pediatric patients demonstrates diverse clinical features and outcomes. TPM3-ALK mutations are associated with favorable prognosis, whereas CLTC-ALK mutations correlate with central nervous system involvement. ATIC-ALK, MYH9-ALK, and TRAF1-ALK mutations are linked to increased relapse risk."

Retrospective data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • ALK • CLTC • NPM1 • TNFRSF8 • TPM3 • TRAF1

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

A Study of Alectinib and Duvelisib in People With Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ALCL) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Non-Hodgkin’s Lymphoma • Oncology

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

Drugs-SNPs: Pharmacogenomics IND EXEMPT SNP Clinical Study - Alectinib and Single Nucleotide Polymorphisms (clinicaltrials.gov) - P2/3 | N=600 | Not yet recruiting | Sponsor: Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P3 | N=71 | Recruiting | Sponsor: Hoffmann-La Roche | N=121 ➔ 71

Biomarker • Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • RET • ROS1

Perforation of the descending colon induced by alectinib in a patient with non-small cell lung cancer: a Case Report. (PubMed, Front Pharmacol) - "While alectinib has been reported to cause serious gastrointestinal perforations, the underlying mechanism remains unclear and warrants further clinical investigation. Clinicians should be vigilant in recognizing and promptly managing this potential complication during alectinib therapy."

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

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

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

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

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

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

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

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 • High Grade Glioma • Infectious Disease • Lymphoma • 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

Lorlatinib therapy in relapsed/refractory ALK+ lymphomas previously treated with tyrosine kinase inhibitors. (ASCO 2025) - "Funded by No funding sources reported 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

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

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

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

Neladalkib (NVL-655), a highly selective anaplastic lymphoma kinase (ALK) inhibitor, compared to alectinib in first-line treatment of patients with ALK-positive advanced non-small cell lung cancer: The phase 3 ALKAZAR study. (ASCO 2025) - P3 | "Additional analyses will be conducted to investigate candidate biomarkers and molecular mechanisms of response and resistance to neladalkib and alectinib. The study is open to accrual."

Clinical • Metastases • P3 data • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

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