Alecensa (alectinib) / Roche - LARVOL DELTA

SHEDDING LIGHT ON PATIENT-REPORTED OUTCOME MEASURE UTILIZATION ACROSS NSCLC THERAPIES (ISPOR 2026) - "Within monotherapies, disease-specific quality-of-life (QOL) measures, particularly EORTC QLQ-C30 (n=11) and EORTC QLQ-LC13 (n=8), were frequently used in trials of ALK inhibitors (e.g., alectinib), PD-L1 inhibitors (e.g., atezolizumab, durvalumab), and PD-1 inhibitors (e.g., nivolumab, and pembrolizumab). Tyrosine kinase inhibitors (e.g., zongertinib, entrectinib) combined disease-specific EORTC QLQ-C30 and generic QOL instruments, such as EQ-5D (n= 4). In contrast, TIGIT inhibitors (e.g. rilvegostomig) and antibody-drug conjugates (e.g. dato-DXd) predominantly utilize PROMIS, which assesses general health and physical and mental functioning rather than QOL (n= 4). PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. Substantial heterogeneity in PRO instrument selection suggests a lack of..."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT

SHEDDING LIGHT ON PATIENT-REPORTED OUTCOME MEASURE UTILIZATION ACROSS NSCLC THERAPIES (ISPOR 2026) - "Within monotherapies, disease-specific quality-of-life (QOL) measures, particularly EORTC QLQ-C30 (n=11) and EORTC QLQ-LC13 (n=8), were frequently used in trials of ALK inhibitors (e.g., alectinib), PD-L1 inhibitors (e.g., atezolizumab, durvalumab), and PD-1 inhibitors (e.g., nivolumab, and pembrolizumab). Tyrosine kinase inhibitors (e.g., zongertinib, entrectinib) combined disease-specific EORTC QLQ-C30 and generic QOL instruments, such as EQ-5D (n= 4). In contrast, TIGIT inhibitors (e.g. rilvegostomig) and antibody-drug conjugates (e.g. dato-DXd) predominantly utilize PROMIS, which assesses general health and physical and mental functioning rather than QOL (n= 4). PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. Substantial heterogeneity in PRO instrument selection suggests a lack of..."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT

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

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

Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1. (PubMed, Br J Cancer) - "Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy."

IO biomarker • Journal • Neuroblastoma • Oncology • Solid Tumor • IFNG • PD-L1

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

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

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

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

CMUH110-REC3-246: Alectinib in Combination With Nivolumab in the Treatment of Recurrent or Refractory HCC Patients Guided With Serum RNase1 and Tumor Expression of PD-L1 (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: China Medical University Hospital | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Feb 2026

IO biomarker • Trial completion • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor • ALK

Real-world safety and tolerability of adjuvant alectinib in resected ALK-positive NSCLC: Results from the Italian ATLAS registry (ELCC 2026) - "AEs leading to dose reduction, interruption, or discontinuation occurred in 9.1%, 5.5%, and 1.1% of patients, respectively. Bradycardia and hypercreatininemia were the most frequent AEs leading to alectinib dose modification.Conclusions In this Italian real-world cohort, adjuvant alectinib showed a favorable safety and tolerability profile, supporting its use in routine practice for resected ALK-positive NSCLC."

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

Real-world safety of ALK inhibitors in non-small cell lung cancer patients: A FAERS disproportionality analysis (ELCC 2026) - "In the cardiac cluster, crizotinib showed marked bradycardia (ROR 12.52, CI 9.57–16.37), with lower but similar signals for alectinib. Gastrointestinal signals were most frequent with ceritinib, while pulmonary disproportionality was observed primarily with lorlatinib, brigatinib, and crizotinib.Conclusions Relative to other NSCLC therapies, ALKis are associated with higher reporting signals across the eye, nervous system, cardiac, musculoskeletal, gastrointestinal, and pulmonary adverse event clusters, with agent-specific disproportionalities being noted. The findings are consistent with ALKi's known safety profiles, emphasizing the importance of corroborating clinical trials with real-world data and the value of pharmacovigilance findings in treatment selection."

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

Skeletal muscle, subcutaneous and intramuscular fat as prognostic biomarkers in TKI-treated fusion-positive NSCLC (ELCC 2026) - "BC parameters were correlated to progression-free survival (PFS) using a Cox model.Results Among 17 pts, 10 ALK positive pts were treated with alectinib and 4 with lorlatinib, while 2 ROS1-positive and 1 NTRK1-positive with entrectinib. Notably, SAT was also related to worse PFS at all time points: T0 (HR 1.02; p=0.046), T1 (HR 1.02; p=0.040), T2 (HR 1.02; p=0.023), and T3 (HR 1.02; p=0.043). No statistically significant changes in BC parameters were observed across time-points (T0-T3), possibly due to the nutritional intervention and limited sample size.Conclusions Despite the preliminary nature of these findings, SMA, SAT and IMAT emerged as potential prognostic biomarkers in fusion-positive NSCLC pts treated with TKIs, highlighting the clinical relevance of body composition assessment and suggesting a pivotal role of targeted interventions, including nutritional support and physical exercise."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • NTRK1 • ROS1

Treatment sequencing after alectinib failure in ALK-positive NSCLC: A Canadian multicentre real-world analysis (ELCC 2026) - "We evaluated treatment sequencing, durability and clinical outcomes of lorlatinib (L) or brigatinib (B) treatments immediately after A progression.Methods In a Canada-wide multicentre retrospective cohort study of advanced ALK-positive NSCLC treated with either L or B following A progression, endpoints included overall survival (OS), progression-free survival (PFS), time to treatment discontinuation (TTD), and subsequent treatment lines. This clinically relevant data informs real-world sequencing decisions beyond PFS alone. Durability of benefit, not only response duration, should guide post-A treatment decisions in ALK-positive NSCLC."

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

Rare and non-canonical ALK fusion in advanced NSCLC: Heterogeneous clinical outcomes with ALK inhibitors (ELCC 2026) - "A 22-year-old patient with HIP1–ALK and concomitant TP53 mutation experienced rapid disease progression, with limited benefit from sequential ALK TKIs (PFS 8 months with alectinib and 4 months with lorlatinib) and fatal outcome. In contrast, the patient harboring NCOA1–ALK is experiencing durable disease control with first-line alectinib since February 2023.Conclusions In a real-world setting, NGS identifies a non-negligible proportion of rare and non-canonical ALK fusions associated with markedly heterogeneous clinical outcomes. These findings suggest that rare ALK rearrangements may represent biologically distinct entities with variable sensitivity to ALK TKIs and support comprehensive molecular profiling and cautious interpretation beyond the canonical EML4–ALK paradigm."

Clinical • Clinical data • Heterogeneity • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • CAPN1 • EML4 • HIP1 • NCOA1 • TP53

TRI-611, a development stage molecular glue degrader of ALK, promotes the degradation of TKI-resistant ALK fusion proteins and leads to regression of ALK TKI-refractory tumors (AACR 2026) - "Finally, we show that TRI-611 leads to the regression of an EML4-ALK mutant primary patient-derived xenograft isolated from a patient that had progressed on prior alectinib and lorlatinib. These data demonstrate the potential of TRI-611 to address a key liability of ALK TKIs that all target the same site on ALK and support the development of TRI-611 in all ALK+ NSCLC patients, including patients with wild-type ALK kinase domain and those with acquired TKI resistance mutations."

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

Nautika1: Clinical Outcomes and Pathologic Regression With Neoadjuvant Alectinib in Resectable Stage IB-IIIB ALK + NSCLC (IASLC-WCLC 2025) - P2 | "Neoadjuvant alectinib was well tolerated with no new safety signals. Conclusions : Neoadjuvant alectinib achieved clinically meaningful MPR/pCR rates with no new safety signals, and can be added to ALINA as a promising perioperative approach for patients with resectable, stage IB-IIIB ALK+ NSCLC."

Clinical • Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • KRAS • NTRK • ROS1

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 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P4 ➔ P3

Phase classification • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

A patient with advanced ALK-positive NSCLC at diagnosis with a follow up of >7 years and multiple lines of systemic therapy and local ablative therapy (DKK 2026) - "He was initially treated with bevacizumab, carboplatin and pemetrexed outside our institution. Due to multiple side effects the therapy was switched to pembrolizumab after the 1st cycle...The patient started alectinib in 11/2018 with rapid clinical improvement and a partial response after 6 weeks...Side effects were hypercholesterinemia (>600 gm/dl) and hypertriglyceridemia (>400 mg/dl) requiring therapy with rosuvastatin and ezetrol...NGS again showed no new on/off-target resistance pattern and he continued lorlatinib...The patient was included in the Early Access Program of NVL-655 currently available at 6 European sites. He started therapy in 06/2025 in Paris and responded in PET-CT after six weeks. He had no side effects CTC >1° and is continuing the therapy."

Clinical • IO biomarker • Metastases • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EML4 • NKX2-1 • PD-L1 • TP53

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P4 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) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Jul 2028 | Trial primary completion date: Dec 2028 ➔ Jul 2028

Trial completion date • Trial primary completion date • 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

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

SIPA1L3 loss induces TKI resistance via Rap1-MAPK activation in ALK-/RET-fusion positive NSCLC (AACR 2026) - "Still, in a significant number of cases, the mechanism of resistance remains unknown.To discover additional potential resistance mechanisms, we conducted a genome-wide CRISPR/Cas9 screening under floating culture condition culture conditions in CCDC6-RET fusion positive LC2/ad cells treated with selpercatinib or pralsetinib for nine days. Furthermore, loss of SIPA1L3 also conferred ALK-TKI resistance in the ALK-fusion H3122 cell line, accompanied by increased Rap1-GTP expression. Co-treatment with alectinib and avutometinib effectively suppressed DTP formation.In conclusion, this study identifies SIPA1L3 as a critical mediator of ALK- or RET-TKI resistance in NSCLC from genome-wide CRISPR screening and underscores the therapeutic potential of avutometinib in combination with ALK-/RET-TKIs to overcome drug-tolerant persistence and improve treatment outcomes in ALK-/RET-rearranged NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CCDC6 • RET