Ladarixin + Sotorasib for Advanced Non-Small Cell Lung Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: NYU Langone Health
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a phase I/II, open-label, study of twice-daily oral ladarixin with sotorasib in participants with advanced KRASG12C mutant non-small cell lung cancer (NSCLC).
What data supports the idea that Ladarixin + Sotorasib for Advanced Non-Small Cell Lung Cancer is an effective drug?The available research does not provide any data on the effectiveness of Ladarixin + Sotorasib for Advanced Non-Small Cell Lung Cancer. All the studies listed focus on treatments for rheumatoid arthritis, not lung cancer. Therefore, there is no information here to support the effectiveness of Ladarixin + Sotorasib for this specific type of cancer.123713
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You cannot use systemic anticancer agents, drugs known to be moderate or strong CYP3A4 inhibitors or inducers, or drugs metabolized by CYP2C9 with a narrow therapeutic index within specific timeframes before starting the trial. Herbal drugs and supplements with similar properties are also prohibited. Some medications may be allowed at the investigator's discretion with approval. Please consult with the trial team for guidance on your specific medications.
What safety data exists for Ladarixin + Sotorasib in treating advanced non-small cell lung cancer?The provided research does not contain specific safety data for the combination of Ladarixin (also known as DF-2156A, DF-2156Y, LDX, Meraxin) and Sotorasib (also known as Lumakras, AMG-510) in treating advanced non-small cell lung cancer. The studies focus on other treatments and their adverse events, such as ALK inhibitors and BRAF/MEK inhibitors, but do not mention Ladarixin or Sotorasib. Therefore, specific safety data for this combination treatment is not available in the provided research.45101115
Is the drug Ladarixin + Sotorasib a promising treatment for advanced non-small cell lung cancer?Yes, Sotorasib is a promising drug for advanced non-small cell lung cancer with a specific KRAS G12C mutation. It has shown positive results in clinical trials, improving patient outcomes and offering a new treatment option for those who have already tried other therapies.6891214
Eligibility Criteria
Adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRASG12C can join this trial if their disease worsened after anti-PD-1 therapy and/or chemotherapy. They must be able to take pills, have no serious heart issues or infections, not be pregnant or breastfeeding, agree to use contraception, and cannot have had certain other treatments recently.Inclusion Criteria
I am 18 years old or older.
I am fully active or can carry out light work.
My lung cancer cannot be cured with surgery or radiation.
My cancer progressed after treatment with anti-PD(L)-1, with or without chemo.
My lung cancer diagnosis has been confirmed by a lab test.
I can swallow and keep down pills.
My tumor has the KRASG12C mutation.
Exclusion Criteria
I have been treated with KRAS inhibitors before.
I have had lung conditions that needed steroid treatment.
I have heart problems that affect my daily activities.
I am not taking medications that are sensitive to changes in how they are broken down by my body.
I haven't taken any cancer drugs or experimental drugs within the last month.
I haven't taken any strong medication that affects liver enzymes in the last 14 days.
I started treatments like erythropoietin or G-CSF less than 2 weeks before beginning the study drug.
I have had a bone marrow or organ transplant from another person.
I have had serious eye inflammation or related conditions in the last 6 months.
I have had a blockage in my bile ducts due to cancer within the last 6 months, but I have a working biliary stent.
I have an active hepatitis B or C infection.
I am not allergic to ladarixin, sotorasib, or their ingredients.
Treatment Details
The study is testing the combination of two oral drugs: ladarixin and sotorasib. It's for patients whose NSCLC carries the KRASG12C mutation. The trial aims to see how well these drugs work together when taken twice daily by people who've already tried some other treatments.
1Treatment groups
Experimental Treatment
Group I: Advanced NSCLC PatientsExperimental Treatment2 Interventions
Patients with KRASG12C mutant NSCLC will receive ladarixin and sotorasib in combination.
Find a clinic near you
Research locations nearbySelect from list below to view details:
NYU Langone HealthNew York, NY
NYU Langone HealthNew Hyde Park, NY
NYU Langone HealthGarden City, NY
NYU Langone HealthMineola, NY
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Who is running the clinical trial?
NYU Langone HealthLead Sponsor
References
A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. [2021]We examined how combination DMARD therapies and TNF inhibitors therapies plus MTX (TNF/MTX) affect clinical and radiological outcomes compared with MTX monotherapy in early RA.
Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide-anti-TNF-alpha versus methotrexate-anti-TNF-alpha. [2021]To compare the efficacy and safety of leflunomide (LEF)-anti-TNF-alpha combination therapy to methotrexate (MTX)-anti-TNF-alpha combination therapy in a group of patients with active rheumatoid arthritis (RA). We have recruited 120 patients with RA with a high disease activity despite being treated with MTX (15 mg/week) or LEF (20 mg/die) for 3 months, without side effects. In each of these patients, therapy with either MTX or LEF was continued and randomly combined with an anti-TNF-alpha drug: etanercept, infliximab, or adalimumab. Patients were assessed at study entry and at 4, 12, and at 24 weeks. The efficacy endpoints included variations in the DAS28-ESR and the ACR20, ACR50, and ACR70 responses. At each visit, any side-effect was recorded. There were no statistically significant differences in the DAS28 variations and in the ACR responses between the two groups or among the six subgroups. The number of discontinuation due to the appearance of serious side effects was higher, but not statistically significant, in the LEF-anti-TNF-alpha group than in the MTX-anti-TNF-alpha group. Other adverse events that did not necessitate the discontinuation of therapy occurred much more frequently in patients treated with MTX than in those treated with LEF. Anti-TNF-alpha drugs can be used in combination not only with MTX, but also with LEF, with the same probability of achieving significant clinical improvement in RA patients and without a significantly greater risk of serious adverse events. In contrast, it seems that combination therapy with LEF-anti-TNF-alpha is more readily tolerated than combination therapy with MTX-anti-TNF-alpha.
Safety and effectiveness of 6 months' etanercept monotherapy and combination therapy in Japanese patients with rheumatoid arthritis: effect of concomitant disease-modifying antirheumatic drugs. [2022]To assess real-world safety, tolerability, and effectiveness of etanercept monotherapy, etanercept plus methotrexate (MTX), or etanercept plus other disease-modifying antirheumatic drugs (DMARD) in Japanese patients with active rheumatoid arthritis (RA) despite previous treatment with DMARD.
BRAF/MEK Inhibitor Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events and Potential Drug Interactions. [2018]BRAF/MEK inhibitor therapy improves outcomes in BRAF V600E- and V600K-mutated unresectable or metastatic melanoma. However, these regimens are associated with adverse events (AEs) that may lead to unnecessary drug modifications and discontinuations or potentially serious sequelae. In addition, drug-drug interactions (DDIs) may result in AEs or altered therapeutic efficacy. .
The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. [2020]Background: A total of 2%-7% of non-small cell lung cancer (NSCLC) patients have anaplastic lymphoma kinase (ALK) mutations. At present, three or more generations of ALK inhibitors have been used for ALK-positive NSCLC treatment, including crizotinib, alectinib, ceritinib, and brigatinib. Although most adverse events (AEs) of ALK inhibitors are grades 1 to 2 and generally can be well tolerated, serious adverse events (SAEs) of ALK inhibitors lack data analysis, and the lung toxicity of ALK inhibitors needs attention. Thus, we performed this meta-analysis to evaluate the safety of ALK inhibitors, especially in terms of drug-related SAEs. Methods: A total of 19 studies from 4 databases (PubMed, Science Direct, ClinicalTrials.gov and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed with the STATA 14.0 software. We analyzed the incidences of total AEs, total SAEs and SAEs for different ALK inhibitors. Results: AEs of the ALK inhibitors occurred in almost all participants, and SAEs occurred in more than 20% of the participants. For ceritinib and brigatinib, SAEs occurred in more than 40% of the participants. Alectinib is most likely the safest of the two generations of ALK inhibitors. Generally, the ALK inhibitors showed significant lung toxicity. Conclusion: In conclusion, attention should be focused on ALK inhibitor-related SAEs, especially lung toxicity. According to this meta-analysis, alxectinib seems to be the safest ALK inhibitor. Physicians should focus on the related SAEs when prescribing ALK inhibitors.
Sotorasib Edges Closer to Approval. [2021]The KRASG12C inhibitor sotorasib continues to impress in non-small cell lung cancer: In the phase II CodeBreak 100 trial, the agent elicited responses in more than a third of patients and led to a median progression-free survival of almost 7 months. Based on these results, Amgen has filed for the drug's approval with the FDA and the European Medicines Agency.
Comparison of the efficacy and safety of tofacitinib and mavrilimumab in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. [2021]The relative efficacy and safety of tofacitinib and mavrilimumab were assessed in patients with rheumatoid arthritis (RA) presenting an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022]Label="BACKGROUND">Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).
Sotorasib: First Approval. [2022]Sotorasib (LUMAKRAS™) is a RAS GTPase family inhibitor being developed by Amgen for the treatment of solid tumours with KRAS mutations, including non-small cell lung cancer (NSCLC) and colorectal cancer. In May 2021, sotorasib was granted accelerated approval by the US FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This article summarizes the milestones in the development of sotorasib leading to this first approval for KRAS G12C-mutated NSCLC.
Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis. [2022]Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients.
Human leucocyte antigen genotype association with the development of immune-related adverse events in patients with non-small cell lung cancer treated with single agent immunotherapy. [2022]Biomarkers that predict the risk of immune-mediated adverse events (irAEs) among patients with non-small cell lung cancer (NSCLC) may reduce morbidity and mortality associated with these treatments.
Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor. By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA. A clinically relevant objective response rate was observed in patients with KRAS G12C mutation-positive NSCLC during the primary analysis and in an updated analysis of the phase I/II CodeBreaK 100 trial. Furthermore, a clinically relevant response duration was reported in updated analyses of the trial. Sotorasib has a manageable tolerability profile, with permitted dose modifications to manage toxicity. In summary, sotorasib is a promising KRASG12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.
Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review. [2022]To analyze the safety and efficacy of certain biologics DMARDs (Adalimumab, Baricitinib, Pefacitinib and Sirukumab) either used alone or as a combination with MTX for management of rheumatoid arthritis.
Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report. [2023]The efficacy of sotorasib for patients with KRAS G12C-mutated lung cancer with poor performance status (PS) and active brain metastases remains unknown. Here, we present a case in which sotorasib was introduced as the third-line therapy for a patient whose PS worsened due to active multiple brain metastases and disseminated intravascular coagulation (DIC) caused by rapid tumor progression; a marked effect was observed. DIC and PS improved two weeks after the start of the administration, and multiple brain metastases disappeared. The effect lasted only approximately four months due to the development of a new liver metastasis, but sotorasib improved PS and the DIC status was reversed, allowing for further treatment. Sotorasib could be considered for introduction in patients with poor PS.
Unusual Adverse Events in a Patient With BRAF-Mutated Non-Small Cell Lung Cancer Treated With BRAF/MEK Inhibition. [2023]BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment. The patient was able to continue BRAF/MEK inhibition through a coordinated multidisciplinary approach. This case highlights the importance for all clinicians to recognize unusual AEs associated with BRAF/MEK inhibition, particularly in the setting of expanded use for all BRAF V600E-mutated solid tumors.