Alecensa (alectinib) / Roche - LARVOL DELTA

Phase I/II Trial of Alectinib and Bevacizumab in Patients With Advanced, Anaplastic Lymphoma Kinase (ALK)-Positive, Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=11 | Terminated | Sponsor: Massachusetts General Hospital | N=43 ➔ 11 | Unknown status ➔ Terminated; slow accrual

Enrollment change • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A Rollover Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer (clinicaltrials.gov) - P3 | N=200 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2026 ➔ Oct 2025 | Trial primary completion date: Jun 2026 ➔ Oct 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Oncology

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

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

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

Identifying brain-penetrant small-molecule modulators of human microglia using a cellular model of synaptic pruning. (PubMed, Neuropsychopharmacology) - "For example, identified drugs such as the tyrosine kinase inhibitors lapatinib, alectinib, and lazertinib and the epigenetic modulator vorinostat have been approved for various cancer treatments and are being investigated for other indications; however, they have not been extensively studied in patients for neurodevelopmental and neurodegenerative disorders. These potential disease-modifying agents represent high-priority candidates for repositioning studies in neurodevelopmental, neuroinflammatory, or neurodegenerative disorders."

Journal • CNS Disorders • Oncology

Case Report: Severe brigatinib-induced pneumonitis in a patient with EML4-ALK+ metastatic non-small cell lung adenocarcinoma. (PubMed, Front Oncol) - "The workup for alternative etiologies of respiratory distress was unrevealing, and the patient was treated for presumed brigatinib-induced pneumonitis with high-dose methylprednisolone. This case demonstrates high-grade, rapidly progressive brigatinib-induced pneumonitis with prompt clinical improvement after steroids and a marked disease response without recurring toxicity after treatment with an alternative ALK TKI, alectinib."

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

Progression and expansion of ALK inhibitors against NSCLC: A dual target approach. (PubMed, Eur J Med Chem) - "Since the ALK inhibitors such as Crizotinib, Ceritinib, Brigatinib, Alectinib and Lorlatinib, was endorsed for the treatment of advanced NSCLC linked to ALK gene rearrangement. The aim of this review is to summarize the introduction to ALK and the synergy between ALK and other anti-tumor targets, recent developments in the synthesis of various dual inhibitors of the ALK. We also thoroughly discussed their design concepts, structure-activity relationships (SARs), preclinical and clinical data as well as in silico studies to provide ideas for further development of novel ALK based dual inhibitors."

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

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

Multimodal imaging and functional outcomes of choroidal metastases from non-small cell lung cancer treated with targeted therapy. (PubMed, Eur J Ophthalmol) - "Systemic evaluation confirmed ALK-rearranged NSCLC (case 1) and EGFR-mutated NSCLC (cases 2 and 3), leading to first-line treatment with Alectinib and Osimertinib, respectively. Microperimetry demonstrated distinct functional alterations based on lesion location.ConclusionsThis series highlights favorable long-term outcomes in NSCLC patients with CMs treated with next-generation TKIs. It underscores the value of multimodal imaging and functional assessments in monitoring disease progression and treatment response, emphasizing the importance of early targeted therapy in optimizing visual outcomes."

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

Efficacy and safety of toripalimab adjuvant therapy of high-risk factors in stage IA2-IB NSCLC without EGFR and ALK mutation after complete resection treatment (TORAT): A prospective, single-arm study (AACR 2025) - "ADUARA study showed that in the IB subgroup of patients with EGFR mutations, postoperative use of osimertinib can reduce the risk of recurrence or death by 61%, ALINA shows that postoperative use of alectinib can reduce the risk of recurrence or death by 79% in IB patients with ALK mutations...Keynote091 shows that pembrolizumab prolongs the DFS effect in postoperative adjuvant therapy (53.6 vs 42.0; HR 0.76)...Exploratory endpoints include the correlation between genomic changes (mutations, copy number changes (CNV), structural changes, etc.), gene expression profiles, and the efficacy of trastuzumab in pre-treatment lesions and peripheral blood, tumor recurrence and peripheral blood during treatment, and the recurrence mechanism of trastuzumab in early NSCLC. 8 of planned 51 patients have been enrolled by December 31, 2024."

Clinical • IO biomarker • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-1

"The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) recommends that alectinib be reimbursed for adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA (according to American Joint Committee on Cancer [AJCC] Cancer Staging Manual seventh edition) ALK-positive non–small cell lung cancer (NSCLC)…" (Ottawa (ON): Canadian Agency for Drugs and Technologies in Health)

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

ALK-driven NSCLC and radiotherapy - contra (ESTRO 2025) - "To datewe lack evidence from clinical trials of RT-ALK TKIs superiority over standard chemoradiation (CRT) in locally advanced NSCLC.The sole trialdedicated to molecularlyselected patients-the NRG/RTOG1306 trial-evaluated erlotinib and crizotinib as a 3-month induction preceding standard CRT in stage III EGFR-positive or ALK-positive NSCLC.The underpowered trialrevealed disappointing results.The median loco-regional PFS was 14.7months in ALK- positive NSCLC patients treated with induction crizotinib and the median OS was not assessed in this cohort.Serious adverse events occurred in 44% of ALK-positive patients receiving induction crizotinib (pneumonitis, thromboembolic events, esophagitis) and in29% of ALK-positive patients receiving CRT alone (pneumonia, atrial fibrillation)...Alectinib demonstrated superior IC activity and significantly delayed CNS progression versus crizotinib, irrespective of prior CNS disease or RT.In the phase III CROWN study lorlatinib, the 3 rd..."

Atrial Fibrillation • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Otorhinolaryngology • Pneumonia • Respiratory Diseases • Solid Tumor • EGFR • EML4 • MET • STAT3

ALK-driven NSCLC and radiotherapy - pro (ESTRO 2025) - "LAURA selected patients with common mutations in EGFR due to the availability of a well-tolerated and efficacious agent (osimertinib), but the findings of this study are likely to be transferable to other such settings...eg. brigatinib, alectinib. A small retrospective series published recently suggests that consolidation ALK-targeted therapy may be more beneficial than durvalumab and no treatment in the scenario where an ALK rearrangement has been identified in the tumour. Prospective evidence is awaited from the ongoing phase 2 BOUNCE trial and phase 3 HORIZON-1 trials, although some patients may ask about off-license use of ALK-targeted therapies in the interim. This presentation will discuss the completed and ongoing studies in the 'ALK-positive' NSCLC chemoradiation setting and explore the implications of these data."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • EML4

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 • Brain Cancer • Infectious Disease • Lung Cancer • Oncology • Pain • Pneumonia • Respiratory Diseases • Solid Tumor

Advancing targeted therapies in oncology: The role of alectinib in managing ALK-positive non-small cell lung cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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 | "Clinical Trial Registration Number: NCT04774718 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

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) - "Clinical Trial Registration Number: jRCT2091220364 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P2 data • Oncology • Pediatrics • Solid Tumor

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 | "Clinical Trial Registration Number: NCT06765109 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Clinical relevance of starting alectinib at a reduced dose in patients with ALK-positive non-small cell lung cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Real-world comparative outcomes of alectinib and brigatinib in ALK-positive non–small cell lung cancer: A retrospective cohort analysis using HIRA data. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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