Alecensa (alectinib) / Roche - LARVOL DELTA

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Precision medicine in colorectal cancer: Personalizing treatment for improved outcomes? (ESMO-GI 2025) - "Other MTT: KRAS G12C inhibitor + Cetuximab (N=18), pan-RAS inhibitor for KRAS G12Cm (N=1), Encorafenib + Cetuximab (N=14) and Dabrafenib + Trametinib (N=1) for BRAF V600Em, Trastuzumab Deruxtecan (N=3) and Tucatinib + Trastuzumab for HER2m/a (N=1), Trametinib for MEKm (N=2), anti LGR5-EGFR bispecific antibody for EGFRm (N=1), Niraparib + Dostarlimab for ARID1Am (N=1), Alectinib for ALKf(N=1) and Inavolisib for PIK3CAm (N=1). Despite no obvious OS benefit of MTT due to small pts number and late MTT lines, this study highlights the different potential targetable MA in 28.9% of pts excluding non G12C RASm. Impact of novel RAS inhibitors and other MTT might change mCRC precision medicine."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • ALK • ARID1A • BRAF • KRAS

Successful pembrolizumab treatment in a patient with ALK-positive lung adenocarcinoma: A case report and literature review. (PubMed, Medicine (Baltimore)) - "Few case reports have described the successful treatment of ALK-positive lung cancer with immune checkpoint inhibitors. We herein present a rare case of ALK-positive lung adenocarcinoma that responded to pembrolizumab monotherapy as the 8th-line treatment."

Journal • Review • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • PD-L1

PHARMACEUTICAL BENEFITS ADVISORY COMMITTEE (PBAC) MEETING OUTCOMES MAY 2025 PBAC MEETING: Alecensa for NSCLC (Pharmaceutical Benefits Scheme (PBS)) - "The PBAC considered alectinib would be cost-effective and that the uncertainties with the survival benefit estimated in the economic model would be mitigated, with a lower price for alectinib and with the updated inputs incorporated into the economic mode...The PBAC considered that consistent with other high-cost adjuvant listings (e.g. osimertinib, immune checkpoint inhibitors), re-treatment in the metastatic setting should not be permitted..."

Reimbursement • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A rare case of ALK-positive histiocytosis with neurological involvement in a 70-year-old woman successfully managed with partial resection and alectinib. (PubMed, Int Cancer Conf J) - "Herein, we report a case of a 70-year-old woman diagnosed with ALK-positive histiocytosis involving the nervous system, successfully treated with partial surgical resection and alectinib administration. To the best of our knowledge, this is the oldest patient reported with this condition with nervous system involvement, expanding our understanding of its clinicopathological spectrum."

Journal • Oncology • ALK

Case Report: Metastatic colorectal cancer with ALK-CEP44 fusion and rapid resistance development. (PubMed, Front Oncol) - "We report a case of metastatic CRC with an ALK-CEP44 fusion not previously described in this tumor type, associated ALK overexpression, a notable clinical response to the ALK inhibitor alectinib, and rapid development of multiple ALK resistance mutations...ALK-targeted therapy may provide benefit in selected CRC cases with atypical ALK alterations, even when the oncogenic role is uncertain. Comprehensive molecular profiling and timely therapeutic decisions are essential in managing such rare and complex cases."

Journal • Colorectal Cancer • Hepatology • Liver Failure • Oncology • Solid Tumor

Successful use of enteric alectinib in a critically ill patient with metastatic ALK-adenocarcinoma: A case report. (PubMed, Pulmonology) - "The patient was discharged and sustained partial response was observed at six months. This highlights the potential for TKI therapy even in critically ill patients."

Journal • Critical care • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Case Report: Successful late-line pralsetinib treatment in an ALK-rearranged lung adenocarcinoma patient with KIF5B-RET fusion resistant to alectinib. (PubMed, Front Genet) - "This case highlights KIF5B-RET fusion as a potential resistance mechanism post alectinib treatment and suggested = pralsetinib, a RET inhibitor, as a viable therapeutic option in this context. These findings contribute to the evolving understanding of resistance management strategies in ALK-rearranged NSCLC."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KIF5B • RET

Drug Repurposing for Targeting ISL LIM Homeobox 2 in Treatment of Endometriosis: A Computational Study. (PubMed, Int J Fertil Steril) - "Although these six drugs appear to be promising candidates for modulating endometriosis, Ivermectin is more likely to effectively inhibit ISL2."

Journal • Endometriosis • Gynecology • Women's Health

Oncogenic ALK fusion in rare subtype of small intestine metastasis from occult lung cancer. (PubMed, Lung Cancer Manag) - "Following 7 months of Alectinib treatment, the patient's clinical evaluation showed stable disease. This is the first report of intestinal metastases from lung cancer with ALK fusion. Our findings indicate that a comprehensive approach, including histopathological examination and genetic testing, is necessary to diagnose and treat intestinal metastases from lung cancer accurately."

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

WHEN TARGETED THERAPIES BACKFIRE: A CASE OF ALECTINIB-INDUCED LUNG INJURY (CHEST 2025) - No abstract available

Clinical • Respiratory Diseases

Alectinib enhances response to RBM39 degradation via SRPK1 inhibition in high-risk neuroblastoma (EACR 2025) - "Indisulam, a potent degrader of RNA Binding Motif 39 (RBM39), disrupts RNA splicing and affects multiple cellular pathways. Our findings highlight that targeting complementary RNA splicing components SRPK1 and RBM39 offers a promising strategy for enhancing therapeutic efficacy and improving outcomes in high-risk neuroblastoma. This approach represents a potential advancement in the treatment of this challenging paediatric cancer."

Neuroblastoma • Oncology • Pediatrics • Solid Tumor • ALK • MYCN • RBM39 • SRPK1

Patient-Derived Glioma Organoids Resist Standard Therapies but Respond to Targeted Inhibition (EACR 2025) - "Despite this, the standard of care (SOC)—maximal surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy—has seen little advancement...Screening of common chemotherapeutic compounds revealed that SOC TMZ and other commonly used treatments had little effect on viability, whereas gefitinib showed a notable impact. In conclusion, while patient-derived glioma organoids present limitations in proliferative capacities and biobanking efficiency that must be addressed for clinical implementation, they remain an invaluable preclinical tool. As demonstrated in this work, the combination of organoids with bioinformatics tools like DiSCoVER establishes a potent platform for testing novel therapeutic strategies in the context of untreatable cancers such as gliomas."

Clinical • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • IDH1

The Food-effect on Alectinib Pharmacokinetics (clinicaltrials.gov) - P=N/A | N=10 | Completed | Sponsor: The Netherlands Cancer Institute | Active, not recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Oct 2024 | Trial primary completion date: Mar 2025 ➔ Oct 2024

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

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

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

Chugai Files for Additional Tumor-Agnostic Indication of Alecensa for ALK Fusion / Rearrangement Gene-Positive Solid Tumors Including Pediatric Patients (Chugai Press Release) - "Chugai Pharmaceutical Co., Ltd...announced that it has filed a regulatory application with the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of its anti-cancer agent/ALK inhibitor Alecensa (generic name: alectinib) for ALK fusion / rearrangement gene-positive unresectable advanced or recurrent solid tumors, including pediatric patients...The application for this additional indication is based on the results of the TACKLE study..."

Japan filing • Non Small Cell Lung Cancer • Solid Tumor

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

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

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