Lorbrena (lorlatinib) / Pfizer, CStone Pharma - LARVOL DELTA

Long-Term Safety of Lorlatinib After 7 Years in CROWN: Kinetics, Management, and Correlations With Efficacy (IASLC-WCLC 2026) - P3 | "Methods : Patients were randomized 1:1 to receive lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. With a mDOT of 62.6 months, AE onset and AE-related treatment modifications occurred mainly within the first 24 months, and AE-related discontinuations remained infrequent with prolonged exposure. These findings support long-term use of lorlatinib and highlight the importance of proactive AE management early in treatment to optimize sustained treatment benefit."

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

Final Biomarker and Efficacy Analyses of Lorlatinib in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer in a Phase 2 Study. (PubMed, J Thorac Oncol) - "After 5 years of follow-up, final analyses from this phase 2 study further supported substantial activity and prolonged OS with lorlatinib in treatment-naive and previously treated patients with ALK-positive advanced NSCLC, regardless of the biomarker subgroups. Resistance mechanisms in treatment-naive patients did not include emergence of ALK mutations."

Biomarker • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • TP53

Lorlatinib Continuation Study (clinicaltrials.gov) - P4 | N=76 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Dec 2026 ➔ Oct 2029 | Trial primary completion date: Dec 2026 ➔ Oct 2029

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

Patient-reported outcomes from the randomized phase 3 CROWN study of first-line lorlatinib versus crizotinib in advanced ALK-positive non-small cell lung cancer. (PubMed, Lung Cancer) - "Patients receiving first-line lorlatinib or crizotinib showed improvements and delayed deterioration in QoL, functioning, and several symptoms. Alongside the previously reported significantly longer progression-free survival and higher intracranial response rates for lorlatinib versus crizotinib, these data further support the use of lorlatinib over crizotinib in patients with advanced ALK-positive NSCLC with/without baseline brain metastases and provide evidence of several QoL improvements with lorlatinib when used in the first-line setting."

Journal • P3 data • Patient reported outcomes • Anorexia • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Insomnia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Respiratory Diseases • Sleep Disorder • Solid Tumor • ALK

Neurologic Burden, Treatment Patterns, and Outcomes in NSCLC Presentingwithcns Metastases: A Retrospective Cohort From Colombia (IASLC-WCLC 2026) - "CNS-penetrant tyrosine kinase inhibitors (TKIs) were defined as osimertinib, alectinib, or lorlatinib...Forty-four patients received systemic therapy, 39 received CNS-directed radiotherapy, and 20 received CNS-penetrant TKIs; 5 received bevacizumab, including 2 in combination with CNS-penetrant TKIs...CNS-penetrant TKIs showed a consistent signal of clinical benefit across survival outcomes. These findings underscore the need for rapid neurologic evaluation, coordinated multidisciplinary care, and timely access to effective CNS-active therapies."

Retrospective data • CNS Disorders • Cognitive Disorders • Epilepsy • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR

Real-World Use of ALK Inhibitors in Advanced Non-Small Cell Lung Cancer: A Multicenter Study in Kazakhstan (IASLC-WCLC 2026) - "Methods : A retrospective, multicenter cohort study was conducted across oncology centers in Kazakhstan, including patients with ALK-positive non-small cell lung cancer (NSCLC) treated with alectinib, brigatinib, or lorlatinib in routine clinical practice. Mortality was numerically higher among patients with CNS metastases compared to those without ( 9.1% vs 4.7%; p=0.31 ), although this difference did not reach statistical significance.At the time of data cutoff, the majority of patients remained on treatment, and median progression-free survival (PFS) had not been reached . Conclusions : his large real-world multicenter cohort from Central Asia demonstrates a substantial burden of CNS metastases and frequent use of sequential ALK inhibitor therapy in ALK-positive NSCLC.Baseline CNS involvement appears to define a clinically more challenging subgroup, associated with a more intensive treatment trajectory and greater reliance on later-line therapies.These findings..."

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

Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study. (PubMed, J Clin Oncol) - "First-line lorlatinib improved PFS outcomes and reduced CNS progression versus crizotinib in patients with advanced ALK-positive non-small-cell lung cancer with or without brain metastases at baseline. Half of all CNS AEs resolved without intervention or with lorlatinib dose modification."

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

A post-hoc analysis of the CROWN study in ALK+ NSCLC using AI to predict progression-free survival based on early response (ESMO 2025) - P3 | "Methods The study analyzed 249 evaluable pts treated with lorlatinib (LOR) or crizotinib (CRZ): 70 pts with baseline (BL) brain metastases (BMs) and 179 without. Conclusions AI lesion-level response at FU1 significantly predicted PFS in ALK+ NSCLC. Early BM response and lung radiomics enabled outcome estimation beyond RECIST, showing potential as early prognosticators in trials and practice."

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

Real-World Clinical Outcomes, Healthcare Utilization, and Costs of ALK TKIs in Patients With ALK+ NSCLC: A Claims Analysis (IASLC-WCLC 2026) - "Patients were categorized by the TKI generation: first-generation (crizotinib) or second/third generation (ceritinib, alectinib, brigatinib, lorlatinib). The favorable 1-year OS rate of 97.8% and a manageable adverse event profile further support the real-world effectiveness and value of modern ALK TKIs. These findings underscore the importance of comprehensive payer-level cost-consequence analyses to characterize the full economic and clinical value of targeted therapies in ALK+ NSCLC."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Febrile Neutropenia • Interstitial Lung Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK

Phase I/II ARROS-1 study of zidesamtinib (NVL-520) in ROS1 fusion-positive solid tumours (ESMO 2024) - P1/2 | "Pts had a median of 3 (range: 1-11) prior anticancer therapies, including any ROS1 TKI (99%); lorlatinib (55%), repotrectinib (repo; 21%), or either (67%); ≥2 ROS1 TKIs (69%); and chemo (66%). Zidesamtinib demonstrated encouraging efficacy and durability in pts with pretreated ROS1+ NSCLC, including those who had exhausted available therapies, with ROS1 resistance mutations including G2032R, and/or with CNS mets. Safety was favorable and consistent with the highly ROS1-selective and TRK-sparing design. Ph 2 enrollment is ongoing with registrational intent in pts with TKI-naïve and pretreated ROS1+ NSCLC."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib. (PubMed, JTO Clin Res Rep) - "In patients without CNS metastasis at baseline, the cumulative incidence rate of CNS progression was lower over time in the LOR group compared with the PEM group (p = 0.045), whereas in patients with CNS metastasis at baseline, there were no significant differences in cumulative incidence rate of CNS progression between both groups (p = 0.43). Clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC."

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

Neoadjuvant lorlatinib in stage III NSCLC harboring ALK fusion: A phase 2 multicenter study (LORIN). (ASCO 2026) - P2 | "Funded by National Science Foundation of China, National Science Foundation of China Clinical Trial Registration Number: NCT05740943 Background: While adjuvant alectinib has established itself as the new standard for resected anaplastic lymphoma kinase (ALK) fusion non-small cell lung cancer (NSCLC), there is limited data on neoadjuvant treatment for locally advanced ALK fusion NSCLC. Neoadjuvant lorlatinib unveiled overwhelming pathological response and could lead to high conversion surgery for unresectable stage III disease. Further large-scale prospective trial was warranted to testified such treatment modality."

Clinical • P2 data • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Solid Tumor • ALK

Efficacy and Safety of Ensartinib Combined With Anlotinib in Lorlatinib-Resistant ALK-Positive NSCLC: An Exploratory Analysis (IASLC-WCLC 2026) - "Conclusions : Ensartinib combined with anlotinib demonstrates promising antitumor activity and favorable tolerability in heavily pretreated lorlatinib-resistant ALK-positive NSCLC. These preliminary findings support further validation in larger prospective cohorts with extended follow-up."

Clinical • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • TP53

Sex Differences in Cardiovascular Outcomes Among Patients With Lung Cancer Treated With ALK Inhibitors: A Propensity Score-Matched Analysis (IASLC-WCLC 2026) - "Adult patients with lung cancer treated with ALK inhibitors (alectinib, crizotinib, ceritinib, brigatinib, or lorlatinib) were identified and stratified by sex (male vs female)...Baseline characteristics were well balanced, including age (~60 years), metastatic disease (~43%), and prior chemotherapy, including platinum chemotherapy (~14%) and pemetrexed (~11%)...Conclusions : In this large propensity score-matched real-world analysis, male patients receiving ALK inhibitors had higher risks of arrhythmias and mortality compared with female patients, with no differences in thromboembolic outcomes. These findings suggest sex-specific differences in cardiovascular toxicity associated with ALK-targeted therapy and support tailored risk stratification in patients with NSCLC."

Clinical • Atrial Fibrillation • Congestive Heart Failure • Heart Failure • Lung Cancer • Myocardial Infarction • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism

Prophylactic peptide vaccine targeting resistance mutations in advanced ALK-positive lung cancer: Primary analysis from the ARCHER trial. (ASCO 2026) - P1/2 | "Patients continued their ALK TKI and received ALK-Vac, consisting of synthetic long peptides targeting seven common ALK resistance mutations (I1171T, I1171N, I1171S, L1196M, G1202R, D1203N, E1210K) plus poly-ICLC adjuvant...Concomitant TKIs included alectinib (7/15, 47%), lorlatinib (5/15, 33%), and brigatinib (3/15, 20%)... ALK-Vac was well-tolerated and induced vaccine-specific T cell responses in a minimal residual disease setting, demonstrating feasibility of prophylactic targeting of ALK resistance mutations as an adjunct to TKI therapy and supporting a broader immune-interception framework potentially applicable to other oncogene-driven NSCLC. Comprehensive cfDNA and immune-phenotyping analyses will be reported."

First-in-human • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • IFNG • KRAS

Lorlatinib plus Sacituzumab Tirumotecan with Peripheral ctDNA Guidance as First‑Line Therapy for ALK Fusion‑Positive NSCLC (ChiCTR) - P2 | N=153 | Not yet recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

Circulating tumor DNA • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

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

Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ non-small cell lung cancer: 7-year update from the phase 3 CROWN study. (ASCO 2026) - P3 | "With median PFS yet to be reached after 7 yrs of f/u in CROWN, lorlatinib continues to show unprecedented and highly durable benefit in treatment-naïve pts with advanced ALK+ NSCLC. In pts without a PFS event at 24 mos, the probability of survival without progressive disease at 7 yrs was 79%. Longer f/u showed very few additional PFS events, no new IC progression, and no new treatment-related discontinuation, suggesting long-term substantial benefit with lorlatinib for the majority of pts with advanced ALK+ NSCLC."

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

How to manage radioiodine-refractory thyroid cancer in the era of precision medicine. (PubMed, Drugs Context) - "Three multi-kinase inhibitors have been approved for this indication: lenvatinib and sorafenib as a first-line option and cabozantinib as a second-line option...Thus, additional selective inhibitors have been approved: larotrectinib and entrectinib for NTRK + tumours, selpercatinib and pralsetinib for RET + tumours, and crizotinib, alectinib and lorlatinib for ALK + tumours. Such a personalized approach increases clinical benefit whilst minimizing adverse events. Future studies should focus on the combination of tyrosine kinase inhibitors and immune-checkpoint inhibitors; currently, there is no strong evidence that redifferentiation strategies add clinical benefit in terms of overall survival or progression-free survival."

Journal • Review • Oncology • Solid Tumor • Thyroid Gland Carcinoma • ALK • NTRK

ALKOVE-1: Efficacy and safety of neladalkib in patients with advanced ALK+ NSCLC. (ASCO 2026) - P1/2 | "c Pts with 1 prior 2nd generation ALK TKI (alectinib, n=44; brigatinib, n=2) ± chemo: ORR 48% (22/46) and DOR ≥ 12 m of 74% (95% CI: 48, 88). In this ALK TKI pre-treated data set, neladalkib demonstrated clinically meaningful activity, including in pts with CNS disease, ALK G1202R single or compound mutations, and prior lorlatinib. Encouraging preliminary activity was also observed in TKI-naïve pts. Neladalkib's safety profile was consistent with its ALK-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK

First-line lorlatinib versus crizotinib in Asian patients with advanced ALK-positive NSCLC: 5-year outcomes from the CROWN study. (PubMed, J Thorac Oncol) - P3 | "After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib."

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

Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+ NSCLC (IASLC-WCLC 2025) - P1/2 | "50% of patients received ≥2 (range 1-4) prior ROS1 TKIs, of whom 93% had prior lorlatinib, repotrectinib, and/or taletrectinib. In this pivotal ROS1 TKI pre-treated data set, zidesamtinib demonstrated clinically meaningful activity and durability, including in patients with CNS disease and/or ROS1 G2032R-mutations, and/or in patients who had exhausted available options. Encouraging preliminary activity was also observed in TKI-naïve patients. Zidesamtinib's safety profile was consistent with its highly ROS1-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Solid Tumor • ROS1

Emerging Therapies in Lung Cancer: A Review on Targeted and Immune Based Interventions. (PubMed, Curr Drug Discov Technol) - "In genetically defined NSCLC subsets, targeted therapies such as Osimertinib and Lorlatinib have significantly enhanced progression-free survival. Similarly, immune checkpoint inhibitors like Nivolumab have redefined care standards, particularly in PD-L1-positive tumours...This article also reviews pivotal clinical trials and newly filed patents, reflecting current and emerging commercial interests. The integration of molecular diagnostics and precision therapies is reshaping lung cancer treatment, with prospective directions aiming to overcome resistance and broaden access to innovative therapies worldwide, including from India and other developing regions."

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

Efficacy of MET-TKI in ALK-rearranged,MET-aberrant Advanced NSCLC After Resistance to ALK-TKI (IASLC-WCLC 2026) - "Five patients received crizotinib or ensartinib, while 8 patients received alectinib/lorlatinib combined with savolitinib/vebreltinib/capmatinib. Lung cancer drug-sensitive organoids could offer personalized medication guidance. Further research is needed for further exploration in the future."

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

Additional Trametinib Delays and Overcomes Acquired Resistance to Lorlatinibin ALK-Rearranged Lung Cancer (IASLC-WCLC 2026) - "Conclusions : Our findings suggest that activation of MAPK signaling confers acquired resistance to lorlatinib in ALK -rearranged NSCLC. The combination of lorlatinib with trametinib may offer a promising therapeutic strategy to delay and overcome this resistance, thereby improving treatment outcomes for patients with ALK -rearranged NSCLC."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • MAP2K2