Zykadia (ceritinib) / Novartis, BeOne Medicines - LARVOL DELTA

The immunomodulatory effects of IRF3/7 transcription factors and IL10 in ALK+ anaplastic large cell lymphoma (ALCL) (ASH 2025) - "Ceritinib and Lorlatinib were used as a next generation ALK inhibitors in vitro. Our findings provide evidence that the IRF3 and IRF7 transcription factors are dependent onfunctional cGAS-STING pathway and substantially contribute to anti-tumor immune responses in ALK+ALCL. As NPM/ALK-STAT3-IL10 axis suppresses IRF3/7 - mediated immunomodulatory effects, targetingthis oncogenic axis combined with stimulation of the cGAS-STING pathway may represent an efficienttherapeutic strategy for patients with refractory or relapsing ALK+ ALCL."

Immunomodulating • Lymphoma • Non-Hodgkin’s Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • BSG • CCL2 • CXCL9 • IFNB1 • IGFBP3 • IL10 • IL17A • IL6 • IRF3 • IRF7

ALK -positive lung cancer in India: Real world barriers to precision oncology (ESMO Asia 2025) - "Concomitant mutation with TP53 was seen in 5 patients and with EGFR in 3 patients.In the first line 29(48%) patients received crizotinib,15(25%), ceritinib, 4(6%) alectinib, 6(10%) chemotherapy, 3(5%) lorlatinib. ALK positivity was seen in 10% of NSCLC patients. Survival rates of ALK positive lung cancer has improved significantly with the advent of targeted therapy. CNS progression on first generation TKI remains a challenge as most of the patients are deprived of newer generation TKI due to financial constraints."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • TP53

A multi-centre, real-world study of treatment patterns and outcomes in Anaplastic Lymphoma Kinase (ALK)-rearranged non-small cell lung cancer: The Singapore experience (ESMO Asia 2025) - "ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, ceritinib, alectinib, brigatinib and lorlatinib are among the therapeutic options. ALK TKIs are effective in treating ALK-rearranged NSCLC in the real world setting, mirroring results from randomised trials. Factors to consider in deciding 1L TKI include overall and BM efficacy and toxicities."

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

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response. (PubMed, Haematologica) - "This disruption results in enhanced accumulation of protein aggregates, increased protein polyubiquitination, endoplasmic reticulum stress, and activation of apoptotic pathways. Collectively, our findings support the repurposing of ceritinib in combination with carfilzomib as a translationally relevant and safe strategy to circumvent PI resistance in MM, warranting further clinical investigation in the relapsed/refractory disease setting."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • ALK • IGF1 • IR

MatchMel: Molecular Profiling and Matched Targeted Therapy for Patients With Unresectable Advanced or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=200 | Completed | Sponsor: Melanoma Institute Australia | Active, not recruiting ➔ Completed | N=1000 ➔ 200 | Trial completion date: Dec 2028 ➔ Dec 2025

Enrollment change • Trial completion • Trial completion date • Melanoma • Oncology • Solid Tumor

Cost-utility and budget impact analyses of anaplastic lymphoma kinase inhibitors in Thailand. (PubMed, Sci Rep) - "Sensitivity analyses confirmed that none of the ALK inhibitors were cost-effective compared to chemotherapy. The five-year BIA estimated the budget impact of ceritinib (450 mg/day, 750 mg/day), alectinib (600 mg/day, 1,200 mg/day), and brigatinib at 2,345 (63.81), 3,703 (100.76), 9,830 (267.49), 19,328 (525.92), and 9,502 (258.56) million THB (USD), respectively."

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

Homoharringtonine Shows Efficacy Against Melanoma Leptomeningeal Disease in Preclinical Models Using Patient-Derived Tumor Cells (SNO 2025) - "Among the most potent were ponatinib (EC₅₀: 1.85–4.06×10⁻⁶), sorafenib (9.57–9.77×10⁻⁶), ceritinib (1.84–2.05×10⁻⁶), and homoharringtonine (HHT; 3.63–4.11×10⁻⁸). This study introduces a robust preclinical platform for identifying effective treatments for M-LMD. Our findings highlight the promise of repurposing FDA-approved HHT as a therapeutic option. Future work will focus on elucidating HHT's molecular mechanisms and testing its efficacy across other LMD subtypes, such as those arising from breast and lung cancers."

Preclinical • Tumor cell • Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • CTCs

IGF1R inhibition arrests meningioma growth (SNO 2025) - "Ceritinib demonstrated both preclinical efficacy and promising early clinical activity in a case of radiotherapy-resistant recurrent meningioma. To our knowledge, this represents the first report of clinical efficacy of Ceritinib in meningioma."

Brain Cancer • CNS Tumor • Meningioma • Solid Tumor • IGF1R • IGF2

Ceritinib-ibuprofen synergistic hepatotoxicity: Insights from real-world data and liver organoid models. (PubMed, Toxicology) - "Together, these findings provide a multidimensional understanding of DILI risks associated with ceritinib combination therapies. By integrating pharmacovigilance signals with physiologically relevant in vitro validation, this study highlights the utility of the human liver organoids for elucidating the mechanisms of hepatotoxicity insights and supporting safer prescribing practices, especially when ceritinib is co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen in real-world clinical settings."

Journal • Real-world evidence • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CYP3A4

Homoharringtonine Shows Efficacy Against Melanoma Leptomeningeal Disease in Preclinical Models Using Patient-Derived Tumor Cells (WFNOS 2025) - "Among the most potent were ponatinib (EC₅₀: 1.85–4.06×10⁻⁶), sorafenib (9.57–9.77×10⁻⁶), ceritinib (1.84–2.05×10⁻⁶), and homoharringtonine (HHT; 3.63–4.11×10⁻⁸). This study introduces a robust preclinical platform for identifying effective treatments for M-LMD. Our findings highlight the promise of repurposing FDA-approved HHT as a therapeutic option. Future work will focus on elucidating HHT's molecular mechanisms and testing its efficacy across other LMD subtypes, such as those arising from breast and lung cancers."

Preclinical • Tumor cell • Breast Cancer • Lung Cancer • Melanoma • Solid Tumor • CTCs

Lung Adenocarcinoma Presenting as Superior Vena Cava Syndrome (APSR 2025) - "She was subsequently initiated on Ceritinib 300 mg once daily...Given the patient's Kishi score of 5, the decision to proceed with stenting was considered due to the rapid improvement of symptoms. This case report describes an unusual presentation of advanced adenocarcinoma of the lung with superior vena cava syndrome, which is successfully managed with endovascular stenting."

Cough • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • ALK

MatchMel: Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (clinicaltrials.gov) - P2 | N=1000 | Active, not recruiting | Sponsor: Melanoma Institute Australia | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jul 2027 ➔ Nov 2025

Enrollment closed • Trial primary completion date • Melanoma • Oncology • Solid Tumor

IGF1R inhibition arrests meningioma growth (WFNOS 2025) - P2 | "Ceritinib demonstrated both preclinical efficacy and promising early clinical activity in a case of radiotherapy-resistant recurrent meningioma. To our knowledge, this represents the first report of clinical efficacy of Ceritinib in meningioma."

Brain Cancer • Meningioma • Solid Tumor • IGF1R • IGF2

A Patient-Derived Organoid Biobank of Adamantinomatous Craniopharyngioma as a Platform for Drug Discovery. (PubMed, Adv Sci (Weinh)) - "Additionally, a retrospective analysis of two Ceritinib-treated clinical cases reveals tumor growth with treatment before any possible therapeutic effects are observed, highlighting the need for caution and careful monitoring in treating ACP patients. Collectively, these findings demonstrate that ACP PDOs effectively preserve the biological characteristics of original tumors, thereby providing a valuable platform for developing precision therapies for ACP patients."

Journal • Brain Cancer • CNS Tumor • Oncology

Determination of veliparib metabolic stability in the human liver microsomes using a hydrophilic interaction UPLC-MS/MS quantitative method: greenness assessment with an in silico study for ADME, DEREK alarms and metabolic lability. (PubMed, Analyst) - "Chromatographic differentiation of VLP and ceritinib (internal standard) was conducted utilizing a Luna 3 µm HILIC column (200 Å: 50 × 2 mm, Ea), with an isocratic mobile phase at 0.35 mL min-1 comprising 0.1% HCOOH acid in ACN (90%) and 10 mM NH4COOH in water (pH 3.2) at 10%. Enhancing the metabolic stability can enable more convenient dosage regimens, improving the overall therapeutic experience for patients. In silico research indicates that minor structural alterations to the methoxy group or the pyrrolidine moiety (96% metabolically labile) in the drug design may improve the safety profile and the metabolic stability of novel derivatives relative to VLP."

Journal • Oncology

Identification of plasma cell infiltration-related gene signatures as a novel prognostic model for clear cell renal cell carcinoma. (PubMed, Clin Exp Med) - "Drug sensitivity analysis revealed that tyrosine kinase inhibitors (e.g., ceritinib, imatinib) potently inhibited cancer cell lines in the high PC score group, while inhibitors like acalabrutinib were effective in the low PC score group. Expression of hub genes in KIRC patients was validated using a local cohort and single-cell sequencing. We identified key genes regulating PC infiltration in KIRC and proposed a predictive model that effectively identifies high-risk KIRC patients."

Biomarker • Gene Signature • Journal • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ADAM8 • CD8 • KCNN4 • PPARGC1A • RAG1 • TCIRG1

The TFG-ROS1 Fusion Is an Oncogenic Driver of Human Myeloid Leukemia (ASH 2024) - "We first describe the case of a 39-year-old male with refractory chronic myelomonocytic leukemia (CMML) who did not respond to multiple lines of therapies including Venetoclax plus Azacitidine (VA) and progressed to acute myeloid leukemia (AML) six months later. He failed to respond to induction chemotherapy based on Cladribine and Cytarabine and then received salvage hematopoietic stem cell transplantation (HSCT), but relapsed only half a month after a transient remission post-HSCT...Our in vitro drug toxicity assays demonstrated that ALK/ROS1 inhibitors Ceritinib and Crizotinib were the most effective in treating primary samples of the patient comparing to chemotherapy and VA...In summary, to our knowledge, this is the first characterization of TFG-ROS1 fusion as a novel oncogenic driver of myeloid leukemia. Our analysis elucidate that TFG-ROS1 fusion is a rare but recurrent oncogenic driver of human leukemia through the MEK/ERK signaling axis, and this fusion protein..."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ALK • BCR • PML • ROS1

Targeting IGF1R/Insr Pathway with Approved ALK-Inhibitors Overcomes Proteasome Inhibitor Resistance in Multiple Myeloma (ASH 2023) - "Background: The treatment of multiple myeloma (MM) has advanced rapidly with the discovery of proteasome inhibitors (PIs) bortezomib (BTZ) and carfilzomib (CFZ)...The combination of ceritinib, brigatinib, and entrectinib showed synergistic cytotoxicity with PI BTZ and CFZ and overcame PI-resistance in four different sets of PI-adapted cells... Ceritinib, an FDA-approved drug, overcomes PI resistance in MM by targeting InsR/IGF1R signaling, which is essential for PI resistance in MM. Therefore, ceritinib represents a promising, potential option for the treatment of PI-resistant MM."

Hematological Malignancies • Multiple Myeloma • Oncology • DDIT4 • IGF1 • IGF1R • IR • TSC1

Preliminary Results of Phase 2 Open Label Study of Lorlatinib Monotherapy in Relapsed/Refractory ALK + Lymphomas Previously Treated with Other Tyrosine Kinase Inhibitors (ASH 2023) - P2 | "Median prior therapy lines was 3 (range 2-5); all pts previously received Crizotinib, two pts received also Alectinib and 1 Ceritinib as TKI treatment. Lorlatinib represents a safe and effective salvage therapy for ALK+ Lymphoma patients failing first line TKI treatment. The obtainment of CR at M1 seems to represent a pivotal prognostic factor. Lorlatinib also offers a promising bridging regimen to salvage ASCT especially for ALK+ BCL patients, with high response rates and no additional toxicities, ."

Clinical • Monotherapy • P2 data • B Cell Lymphoma • Cutaneous T-cell Lymphoma • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Large B Cell Lymphoma • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • ALK • EML4 • ROS1

Crizotinib- or Ceritinib-Conjugated Platinum(IV) Prodrugs As Potent Multiaction Agents Inducing Antiproliferative Effects in 2D and 3D Cancer Cell Models. (PubMed, J Med Chem) - "Cisplatin-derived derivatives bearing phenylbutyrate and either crizotinib (complex 3) or ceritinib (complex 7) exhibited the greatest efficacy and selectivity against cancer cells while sparing noncancerous counterparts. Moreover, both agents triggered apoptosis and hallmarks of immunogenic cell death, including calreticulin exposure, ATP and HMGB1 release, and enhanced phagocytosis by macrophages. These findings highlight complexes 3 and 7 as promising multifunctional candidates that combine cytotoxic, anti-invasive, and immune-activating properties, supporting Pt(IV)-kinase inhibitor conjugates as a potential strategy for targeted cancer chemotherapy."

Journal • Oncology • CALR • HMGB1

Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology. (PubMed, Ann Med Surg (Lond)) - "Several ALK inhibitors, like crizotinib, ceritinib, lorlatinib, repotrectinib, and alectinib, have shown different levels of success, but resistance to these treatments is still a big challenge. While ALK inhibitors have shown promise, resistance mechanisms necessitate the development of combination therapies and next-generation inhibitors. Future research should focus on optimizing targeted treatment strategies to improve survival outcomes in pediatric patients with ALK-positive neuroblastoma."

Journal • Review • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • ALK

Association Between ALK Tyrosine Kinase Inhibitor and the Risk of Interstitial Lung Disease and Pneumonitis in Non-Small Cell Lung Cancer Patients: A Systematic Review (ISPOR-EU 2025) - "In the network meta-analysis (NMA), brigatinib was associated with significantly higher risks of both overall ILD and overall pneumonitis than crizotinib (OR=8.87, 95%CI: 1.07 to 73.29; OR=3.43, 95%CI: 1.00 to 11.71, respectively), alectinib (OR=12.78, 95%CI: 1.56 to 104.98; OR=6.09, 95%CI:1.57 to 23.68, respectively) and ceritinib (OR=32.50, 95%CI: 1.05 to 1005.95; OR=21.88, 95%CI: 1.78 to 268.53, respectively). ALK-TKIs increase the risks of both ILD and pneumonitis in NSCLC patients, with brigatinib posing the highest risks among ALK-TKIs."

Clinical • Review • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK

Lorlatinib Monotherapy in Relapsed/Refractory ALK + Lymphomas Previously Treated with Other Tyrosine Kinase Inhibitors: 5-Year Update of a Phase 2 Open Label Monocentric Study (ASH 2024) - P2 | "The median number of prior therapy lines was 3 (range 2-5); all pts had previously received Crizotinib after failing CIT, 2 pts received other TKI treatment with Alectinib and 1 pt with Ceritinib. Additionally, our work confirms that obtaining CR at M1 remains the most important prognostic factor for the durability of response. No relapse was noted after the initial 90 days of treatment."

Clinical • IO biomarker • Monotherapy • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Immunology • Large B Cell Lymphoma • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • ALK • EML4

NPM-ALK Oncoprotein Suppresses Anti-Tumor Immune Responses Partially through Cgas-Sting Pathway in ALK+ Anaplastic Large Cell Lymphoma (ASH 2024) - "Ceritinib was used as a next generation ALK inhibitor in cultured lymphoma cells...STING-deficiency in the T-NHL cells seems to affect the chemokine and cytokine profile in vivo. Modulation of cGAS-STING activity, in addition to ALK inhibition, might represent a novel target for investigational therapy in ALK+ ALCL, and likely other T-cell NHLs."

Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ALK • CXCL10 • CXCL11 • IFNB1 • IL10 • IL17A • IL2 • IL22 • TNFRSF8