Alecensa (alectinib) / Roche - LARVOL DELTA

Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - P3 | "Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.)."

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

Alectinib in combination with bevacizumab as first-line treatment in ALK-rearranged non-small cell lung cancer (ALEK-B): a single-arm, phase 2 trial. (PubMed, Nat Commun) - P2 | "QoL significantly improved from baseline at 12 months and was maintained through 36 months. These findings support the efficacy and safety of alectinib plus bevacizumab and justify further investigation in ALK-rearranged NSCLC."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • ALK

Updated results from the phase III ALINA study of adjuvant alectinib vs chemotherapy (chemo) in patients (pts) with early-stage ALK+ non-small cell lung cancer (NSCLC) (ESMO 2025) - P3 | "AE, adverse event; NE, not evaluable. Conclusions After ≥3 years of follow-up, alectinib continued to show a clinically meaningful DFS benefit and safety data remain consistent with the well-established, manageable profile, reinforcing adjuvant alectinib as standard of care for pts with resected ALK + NSCLC."

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

Alectinib as neoadjuvant treatment in potentially resectable stage III ALK-positive NSCLC: Final analysis of ALNEO phase II trial (GOIRC-01-2020-ML42316). (ASCO 2025) - P2 | "ALNEO study met its primary endpoint, suggesting alectinib as a feasible peri-operative option in resectable locally advanced stage III ALK-positive NSCLC patients. The study was partially supported by Roche S.p.A."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Real World Clinical Outcomes of Resected ALK-Positive Early Stage NSCLC Patients Treated With Alectinib as Adjuvant Therapy (clinicaltrials.gov) - P=N/A | N=800 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2029 ➔ Apr 2029 | Trial primary completion date: Jun 2029 ➔ Oct 2028

Real-world evidence • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Evaluation of Drug-Induced Kidney Injury by Primary Culture of Rat Kidney Tissue Slices Using Oxygen-Permeable Polyolefin Plate with Low Drug Adsorption. (PubMed, Biol Pharm Bull) - "As a result, the InnoCell™ non-treated plates exhibited lower adsorption rates for sunitinib, cyclosporine A, and alectinib than the PDMS plates. Intra-tissue ATP levels were maintained, and immunohistochemical staining of megalin and aquaporin 1 was observed for up to 3 d. Furthermore, exposure to nephrotoxic lipophilic drugs reduced the ATP content in slices compared to that in non-treated slices. These results suggest that the primary culture of rat kidney tissue slices using InnoCell™ non-treated plates is useful for the DIKI evaluation of lipophilic drugs compared with conventional PDMS plates."

Journal • Preclinical • Renal Disease • AQP1

Real-World Safety and Tolerability of Adjuvant Alectinib in Resected ALK-Positive NSCLC: Results from the Italian ATLAS Registry (ELCC 2026) - No abstract available

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

Treatment sequencing after alectinib failure in ALK-positive NSCLC: a Canadian multicentre real-world analysis (ELCC 2026) - No abstract available

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

Final overall survival (OS) and safety analysis of the phase III ALEX study of alectinib vs crizotinib in patients with previously untreated, advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) (ESMO 2025) - P3 | "Safety data were in line with the known safety profile of alectinib. These data continue to support 1L alectinib as a standard of care in pts with advanced ALK + NSCLC."

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

Prospective observational study of brigatinib after alectinib in ALK-positive, non-small cell lung cancer: Efficacy and biomarker analyses from cohort A of the WJOG11919L/ABRAID trial (ESMO 2025) - P=N/A | "Conclusions In this large prospective study of post-alectinib cases, brigatinib appeared to be effective regardless of the presence of ALK resistance mutations, including G1202R. Together with the safety profile consistent with previous reports, these findings suggest that brigatinib may be an appropriate treatment option in this setting."

Biomarker • Clinical • Observational data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • TP53

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • PD-L1 • ROS1

Patterns of Progression with Lorlatinib and Insights into Subsequent Anticancer Therapy Efficacy in Advanced ALK+ NSCLC (IASLC-WCLC 2024) - P3 | "Best Overall Response and Objective Response Rate on First Subsequent Anticancer Therapy Study treatment Lorlatinib Crizotinib First Subsequent Therapy Any ALK TKI (n=23) a Any non-ALK TKI (n=15) b Overall (n=38) Any ALK TKI (n=101) a Any non-ALK TKI (n=8) b Overall (n=109) Objective response rate (95% CI), % c 26.1 (10.2-48.4) 20.0 (4.3-48.1) 23.7 (11.4-40.2) 17.8 (10.9-26.7) 12.5 (0.3-52.7) 17.4 (10.8-25.9) Best overall response, n (%) Complete response 2 (9) 1 (7) 3 (8) 1 (1) 0 1 (1) Partial response 4 (17) 2 (13) 6 (16) 17 (17) 1 (13) 18 (17) Stable disease 1 (4) 3 (20) 4 (11) 23 (23) 0 23 (21) Progressive disease 6 (26) 3 (20) 9 (24) 10 (10) 2 (25) 12 (11) Unknown 3 (13) 5 (33) 8 (21) 9 (9) 4 (50) 13 (12) Not reported, therapy ongoing 7 (30) 1 (7) 8 (21) 41 (41) 1 (13) 42 (39) a Includes alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib. b Includes chemotherapy ± anti-angiogenic, chemotherapy/immunotherapy,..."

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

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

Radioresistant but Alectinib-Responsive Isolated Intramedullary ALK-Positive Histiocytosis. (PubMed, Case Rep Hematol) - "ALK-positive histiocytosis is a recently described distinct clinicopathologic entity. Our case is notable for older age at diagnosis, isolated intramedullary involvement, and radioresistance but later marked targeted-therapy response, thus furthering the understanding of the spectrum of ALK-positive histiocytosis biology."

Journal • Anesthesia • CNS Disorders • Urinary Incontinence • ALK • CD163 • CD68 • KIF5B

Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan. (PubMed, Eur J Cancer) - "Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival."

Journal • Fibrosis • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • BRAF • EGFR • KRAS • MET

A Phase II Trial of Stereotactic Body Radiotherapy (SBRT) in Patients with Stage IV Oncogene-Driven Non-Small Cell Lung Cancer (NSCLC) (ASTRO 2024) - "Most had EGFR driver mutations (n=22, 54.5% on osimertinib), followed by ALK (n=4, on alectinib or lorlatinib), and ROS1 fusions (n=1, on crizotinib). Consolidation SBRT to predominantly the primary lung site in pts with oncogene-driven metastatic NSCLC was not associated with decrease in frequency of DF which constituted 50% of first failures at 1 year. The lack of reduction in DF suggests that SBRT to the primary lung site only is insufficient. Consideration should be given to consolidation SBRT to not only the primary site but also additional original sites of metastasis."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors. (PubMed, Genome Biol) - "This study provides a comprehensive functional atlas of ALK tyrosine kinase domain variants under TKI selection, offering a valuable experimental framework for interpreting resistance-associated variants. Although derived from in vitro models and therefore context dependent, this resource complements existing clinical and genomic knowledge and may aid in the functional interpretation of ALK variants observed in ALK-driven cancers."

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

Hepatotoxicity of new-generation ALK inhibitors versus crizotinib in patients with non-small cell lung cancer: A systematic review and meta-analysis. (PubMed, iScience) - "Alectinib, lorlatinib, and brigatinib are associated with lower risks of hepatotoxicity when compared with crizotinib. Lorlatinib conferred a greater reduction in any grades AST than second-generation inhibitors compared to crizotinib. Our findings suggest that the selection of the ALK inhibitor should be individualized based on the specific profile of hepatotoxicity and their efficacy."

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

Brigatinib Versus Alectinib in ALK-positive Non-small Cell Lung Cancer After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial. (PubMed, J Thorac Oncol) - P3 | "Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3."

Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Final Analysis of Brighstar: LCT With Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC (IASLC-WCLC 2025) - P1, P3 | "Individual patient data from a phase 3 trial of brigatinib vs crizotinib (ALTA-1L, NCT02737501) were retrospectively compared...One patient with grade 3 pneumonitis successfully transitioned to full-dose alectinib after resolution with corticosteroids...Conclusions : Brigatinib with LCT is safe in patients with ALK-rearranged advanced NSCLC and yielded promising results when compared to historical outcomes from brigatinib alone. Patients who received comprehensive LCT had superior outcomes, and baseline ctDNA status and radiological volumetric measurements may serve as prognostic biomarkers for treatment response."

Metastases • Anemia • Endocrine Disorders • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Pneumonia • Renal Disease • Solid Tumor • ALK

ALTA-3: A randomized trial of brigatinib (BRG) vs alectinib (ALC) in crizotinib (CRZ)-refractory advanced ALK+ NSCLC (ESMO Asia 2022) - P3 | "Conclusions At the IA, BIRC PFS was numerically similar between arms. No new safety findings were observed, with safety profiles consistent with known BRG and ALC profiles."

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

Efficacy of Brigatinib in Patients With Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Who Progressed on Alectinib or Ceritinib: ALTA-2 Study. (PubMed, J Thorac Oncol) - P2 | "In ALTA-2, brigatinib demonstrated limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. Median PFS was longer with brigatinib in patients without baseline detectable plasma ALK fusion."

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

Plasma cfDNA analysis of alectinib resistance-related gene alterations in the J-ALEX study. (PubMed, ESMO Open) - "Plasma cfDNA analysis using NGS is feasible and offers insights into alectinib resistance mechanisms. Early detection of resistance-associated mutations may guide personalized treatment strategies. Larger prospective studies are needed to validate these findings."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • MET • NRAS

Phase 3 Trial of Crizotinib vs Observation for Surgically Resected Early-Stage ALK+ NSCLC (IASLC-WCLC 2025) - "Results : Between August 2014 and May 2024, 166 patients were enrolled in the study (of a planned sample size of 168), with enrollment stopped at the time of FDA approval of adjuvant alectinib for resected ALK+ NSCLC. Median duration of crizotinib therapy was 13.5 (IQR 3.4-23.9) months; 19 patients (22%) had crizotinib dose reductions and 21 (25%) discontinued crizotinib due to toxicities. Conclusions : Adjuvant crizotinib does not prolong DFS in resected ALK+ NSCLC."

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor