Alecensa (alectinib) / Roche - LARVOL DELTA

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) - No abstract available

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

Immune-Related Gene Expression Profiling and ALK-TKI Efficacy for Patients With ALK-Rearranged Non-Small Cell Cancer (IASLC-WCLC 2025) - P=N/A | "Conclusions : High CD8 positive T cells infiltration in ALK -rearranged tumor might be associated with longer duration of alectinib efficacy. Anti-angiogenic therapies may enhance anti-tumor immunity and potentially augment the efficacy of alectinib in patients with ALK -rearranged NSCLC harboring low CD8 positive T cells infiltration."

Clinical • Gene expression profiling • IO biomarker • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • ALK • ANGPT2 • CD8 • CDH1 • CXCL10 • CXCL9 • FLT1 • IDO1 • LAG3 • SNAI1

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

Incidence and risk factors of pneumonitis in ALK-rearranged non-small cell lung cancer patients treated with alectinib and thoracic radiotherapy. (PubMed, Transl Lung Cancer Res) - "The combined use of alectinib and TRT significantly increased the risk of TRP. Clinicians should consider the elevated risks and related dosimetric factors when deciding on combination treatment for ALK-rearranged NSCLC patients."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ALK

Alectinib as Adjuvant Therapy in Resected ALK-Positive NSCLC: A Prospective Multicenter Cohort Study in China (IASLC-WCLC 2025) - P | "The safety profile of alectinib as an adjuvant treatment in resected ALK-positive NSCLC in routine clinical practice will be evaluated. The study also explores prognostic factors of recurrence, the healthcare utilization before or after the recurrence, the alterations of ALK or other biomarkers identified between the recurrence and initiation of the next anticancer therapy, and treatment options after recurrence."

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

Economic Burden of Disease Management and Recurrences After Complete Resection of Early-Stage ALK+ Non-Small Cell Lung Cancer (NSCLC) in Spain (IASLC-WCLC 2025) - "Introduction : Adjuvant alectinib has shown a significant benefit with respect to disease-free survival as compared with adjuvant platinum-based chemotherapy (PbCH) in early-stage ALK rearranged non-small cell lung cancer (NSCLC) patients, as well as a mainly low-grade safety profile...Conclusions : Although the number of patients with ALK+ early-stage NSCLC is low, the cost of recurrences (particularly those requiring systemic therapies) represents a substantial burden for the National Health System. Early intervention and the incorporation of more efficacious adjuvant therapies to mitigate recurrence risk are critical to optimize disease management."

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

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

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

A treatment-impact model of alectinib for the prediction of recurrence and associated costs in treating resectable ALK+ non-small cell lung cancer. (PubMed, Lung Cancer) - "Adjuvant alectinib treatment improved population-level clinical outcomes and was predicted to generate cost savings in the US. Predicted alectinib benefits were maximized when all indicated patients were tested for the ALK biomarker."

Journal • 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: Mar 2029 ➔ Nov 2029 | Trial primary completion date: Mar 2029 ➔ Jun 2029

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

ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Ulrik Lassen | Trial completion date: Apr 2025 ➔ Apr 2030 | Trial primary completion date: Apr 2024 ➔ Apr 2029

Trial completion date • Trial primary completion date • Oncology

Optimizing Treatment Sequencing to Maximize Survival in ALK+ Advanced Non-Small Cell Lung Cancer: A Modeling Study (IASLC-WCLC 2025) - "Additional ALKis, such as NVL-655 is under investigation...Results : 1L lorlatinib sequences yielded the longest PFS overall, with ~5 years of additional PFS vs 1L therapy with alectinib or brigatinib (Table and Figure)...Conclusions : Based on current evidence and modeling assumptions, initial treatment with 1L lorlatinib may yield the longest PFS vs 2nd gen TKIs, regardless of types of subsequent treatments. This highlights the importance of initiation of 1L treatment with the longest demonstrated PFS upfront."

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

ALK inhibitors against resistance in non-small cell lung cancer: an 18 year medical arms race. (PubMed, Biochem Pharmacol) - "This review presents a timeline-based approach to understanding how drug development has tackled ALK inhibitor resistance, by integrating key historical developments with resistance mechanisms, and evolving treatment strategies; by discussing the discovery of ALK rearrangements, exploring the molecular underpinnings of resistance, and latest advances in combination therapies and fourth-generation inhibitors. By aligning biological and pharmacological milestones with therapeutic progress this review provides a structured overview of how the field has evolved and where future efforts are directed."

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

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

Enrollment open • Non-Hodgkin’s Lymphoma • Oncology

Short-term results of salvage surgery after immune and target therapies in non-small cell lung cancer. (PubMed, J Thorac Dis) - "Target therapy mutations were anaplastic lymphoma kinase (ALK) rearrangement (treated with alectinib) and epidermal growth factor receptor (EGFR; treated with gefitinib, osimertinib and afatinib) in 8 total cases. Five patients had recurrence and 4 died due to cancer related causes. Salvage surgery after target therapy or immunotherapy resulted to be a possible approach in selected patients."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • EGFR

MTAPloss Is Frequent and Potentially Targetable With PRMT5 Inhibitors in Oncogene-Driven NSCL (IASLC-WCLC 2025) - "CRISPR-engineered MTAP knockout in EGFR + (HCC827) and ALK + (DFCI76) cell lines did not alter sensitivity to respective TKIs, with IC50 values of 0.01 μM for osimertinib (HCC827sgMTAP) and 0.01 μM for alectinib and lorlatinib (DFCI76sgMTAP), all comparable to parental controls. MRTX1719 monotherapy showed IC50 <0.5 μM in 5/7 EGFR + MTAP -deleted models, and <0.16 μM in all 5 ALK + MTAP -deleted lines...Preclinical data suggest that oncogene-driven tumors with MTAP loss are sensitive to single agent PRMT5 inhibitors and that combination TKI and PRMT5 inhibitors may have additive or synergistic antitumor activity. These findings support clinical testing of combined TKI and PRMT5 inhibitors in oncogene-driven MTAP deleted NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • BRAF • CDKN2A • EGFR • HER-2 • KRAS • MTAP • ROS1

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) - No abstract available

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

Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study). (PubMed, Lung Cancer (Auckl)) - "Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced ALK+ non-small-cell lung cancers (NSCLCs). For patients receiving ≥1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3-31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5-18.8) and 19 (95% CI: 2.3-NR) months, respectively. According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced ALK+ NSCLCs, especially when brigatinib was discontinued because of toxicity."

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

A real-world pharmacovigilance analysis of ALK inhibitor-associated pleural and pericardial effusion using the FDA Adverse Events Reporting System (FAERS) database from 2013 to 2024. (PubMed, PLoS One) - "This study highlights the critical need for vigilant pharmacovigilance and a multidisciplinary approach to balance the oncologic benefits of ALK inhibitors against their cardiopulmonary risks. By enhancing awareness and fostering proactive management, these findings aim to support the safe and effective use of ALK inhibitors in treating ALK-rearranged malignancies."

Adverse events • Journal • Real-world evidence • Cardiovascular • Oncology • ALK

Benefits of Adjuvant Alectinib in ALK+ Early-Stage Non-Small Cell Lung Cancer, Recurrences Avoided and Savings for the Spanish Health System (IASLC-WCLC 2025) - "Scenario sensitivity analyses provided a range of 42,3 to 49,3 million euros of savings. Conclusions : The use of adjuvant alectinib in patients with resected ALK+ eNSCLC would substantially reduce the number of recurrences over the next 10 years, resulting in significant cost savings in the management of the advanced disease for the Spanish National Healthcare System."

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

Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC (IASLC-WCLC 2025) - P1/2 | "Most frequently received BAT were tyrosine kinase inhibitors (66.7%; 29.6% investigational agents, 25.9% cabozantinib, 7.4% vandetanib, 3.7% alectinib) and chemotherapy (25.9%)...Conclusions : This RW, multi-center study found that 2L+ treatment with pralsetinib in advanced RET fusion-positive NSCLC was associated with higher ORR and significantly improved OS and PFS compared to BAT, even after adjusting for population differences. Limitations of RW data include missing data and potential unmeasured confounding, which this study aimed to mitigate through rigorous analytical methods."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

A case report and literature review of a pathologic complete response to alectinib in ALK-positive stage IV non-small cell lung cancer. (PubMed, Transl Lung Cancer Res) - "Adjuvant alectinib was continued for unspecified duration due to the lack of available data. This case suggests that local treatment, even in patients with stage IV disease, performed at the time of the best response to systemic therapy, may offer an improvement in progression free survival and perhaps a glimpse of a cure."

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

Neoadjuvant Iruplinalkib in Resectable ALK/ROS1 Fusion-Positive NSCLC: Updated Results of the Exploratory Neo-INFINITY Study (IASLC-WCLC 2025) - "Introduction : Previous trials showed perioperative alectinib and lorlatinib were effective for resectable ALK -positive NSCLC. The trial has progressed to Stage 2. Further data will provide insights into long-term outcomes."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • ROS1

Integrated Molecular Analysis of Advanced NSCLC Depicts Molecular Signatures Associated With Tyrosine Kinase Inhibitors Efficacy (IASLC-WCLC 2025) - "Methods : Samples from patients with advanced NSCLC treated with first-line next-generation TKIs (osimertinib or alectinib) were analyzed for genomic profiling using the Oncomine Comprehensive Assay Plus (ThermoFisher Scientific) panel. Conclusions : The present data suggest the potential role of extended molecular testing to predict benefit of first-line next-generation TKIs in EGFR+ and ALK+ advanced NSCLC. Data from larger populations are warranted to confirm these preliminary findings."

Biomarker • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • MIR331 • MIR423 • MIR455 • TP53

Real-World Impact on Overall Survival of High-Cost Targeted and Immunotherapies in Lung Cancer Patients Under Chile's DAC Program (IASLC-WCLC 2025) - "Patients were evaluated according to the medication received (immunotherapies: Pembrolizumab, Nivolumab; and tyrosine kinase inhibitors: Osimertinib, Alectinib, Crizotinib). This limitation may partially explain variations observed in survival between immunotherapy-treated patient groups and should be considered when interpreting these results.The presence of heterogeneous histologies (adenocarcinoma and squamous cell carcinoma) among patients treated with immunotherapy could influence differential responses and survival outcomes, highlighting the need for future, more detailed subgroup analyses. Additionally, age and cancer staging are critical factors known to influence survival significantly and should be included in subsequent analyses to provide a clearer interpretation of the impact of DAC-funded treatments.Despite these limitations, the data confirm the clinical relevance of DAC by facilitating access to high-cost drugs and underscore the importance of conducting..."

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma