AOA Dx’s Post

Imdelltra (tarlatamab): Mechanism of Action and Clinical Success in Small Cell Lung Cancer https://lnkd.in/dU9kmG4f Tarlatamab is the first and only delta-like ligand 3 (DLL3)–targeting Bispecific T-cell Engager (BiTE®) therapy that activates the patient’s own T cells to specifically attack DLL3-expressing cells. https://lnkd.in/eBzhciYP https://lnkd.in/euHUPXEf On May 16, 2024, the FDA granted accelerated approval to Imdelltra (tarlatamab-dlle) for extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab is a half-life extended bispecific T-cell engager (HLE BiTE) molecule, which binds both DLL3 on cancer cells and CD3 on T cells leading to T-cell–mediated tumor lysis. Imdelltra Prescribing Information https://lnkd.in/eN6sw3f7 The recommended tarlatamab dose is an initial dose of 1 mg administered as an intravenous infusion over 1 hour on Cycle 1 Day 1, followed by 10 mg on Cycle 1 Day 8 and Day 15 then every 2 weeks thereafter until disease progression or unacceptable toxicity. BiTEs Overview https://lnkd.in/eDRAD2mR Could BiTEs be considered an alternative to chimeric antigen receptor (CAR) T-cell therapy? https://lnkd.in/eSvqdAGy #Cancer  #Oncology #Imdelltra #Tarlatamab #BispecificAntibody #BispecificTcellEngager #BiTE #LungCancer  #SmallCellLungCancer #SCLC #ESSCLC #Moffitt #MoffittCancerCenter Moffitt Cancer Center

Imdelltra (tarlatamab): Mechanism of Action and Clinical Success in Small Cell Lung Cancer https://lnkd.in/dU9kmG4f Tarlatamab is the first and only delta-like ligand 3 (DLL3)–targeting Bispecific T-cell Engager (BiTE®) therapy that activates the patient’s own T cells to specifically attack DLL3-expressing cells. https://lnkd.in/eBzhciYP https://lnkd.in/euHUPXEf On May 16, 2024, the FDA granted accelerated approval to Imdelltra (tarlatamab-dlle) for extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab is a half-life extended bispecific T-cell engager (HLE BiTE) molecule, which binds both DLL3 on cancer cells and CD3 on T cells leading to T-cell–mediated tumor lysis. Imdelltra Prescribing Information https://lnkd.in/eN6sw3f7 The recommended tarlatamab dose is an initial dose of 1 mg administered as an intravenous infusion over 1 hour on Cycle 1 Day 1, followed by 10 mg on Cycle 1 Day 8 and Day 15 then every 2 weeks thereafter until disease progression or unacceptable toxicity. BiTEs Overview https://lnkd.in/eDRAD2mR Could BiTEs be considered an alternative to chimeric antigen receptor (CAR) T-cell therapy? https://lnkd.in/eSvqdAGy #Cancer  #Oncology #Imdelltra #Tarlatamab #BispecificAntibody #BispecificTcellEngager #BiTE #LungCancer  #SmallCellLungCancer #SCLC #ESSCLC #Moffitt #MoffittCancerCenter Moffitt Cancer Center

Claims analysis of two datasets showed TNFi treatment in 1st two years after newly Dx breast cancer (n 2216) had no effect on overall survival (OS); but had signif better breast cancer survival (HR 0.28; 0.08–0.98) vs csDMARD Rx. Pts on GC worse OS (HR 2.18)

📃Scientific paper: The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer Abstract: Ubiquitination, a highly adaptable post-translational modification, plays a pivotal role in maintaining cellular protein homeostasis, encompassing cancer chemoresistance-associated proteins. Recent findings have indicated a potential correlation between perturbations in the ubiquitination process and the emergence of drug resistance in CRC cancer. Consequently, numerous studies have spurred the advancement of compounds specifically designed to target ubiquitinates, offering promising prospects for cancer therapy. In this review, we highlight the role of ubiquitination enzymes associated with chemoresistance to chemotherapy via the Wnt/β-catenin signaling pathway, epithelial–mesenchymal transition (EMT), and cell cycle perturbation. In addition, we summarize the application and role of small compounds that target ubiquitination enzymes for CRC treatment, along with the significance of targeting ubiquitination enzymes as potential cancer therapies. Continued on ES/IODE ➡️ https://etcse.fr/DuQC ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Follow-up testing offers significantly more benefits than one-time testing, as it allows for personalized decision-making based on an individual's biomarker levels over time. To this end, we recently published a manuscript in the Lancet journal, eBioMedicine, demonstrating that the trajectory of our 4-marker protein lung panel significantly enhances detection accuracy and leads to earlier lung cancer diagnosis compared to single-time testing. https://lnkd.in/gGktmZbn

🎉 Exciting developments in resectable gastro-oesophageal cancer management! 🎉 The phase III CheckMate 577 study unveils FDA-approved adjuvant nivolumab for operable stage II/stage III E/GEJ cancer, marking a paradigm shift. Key points: ➡️ Combining Therapies for Enhanced Responses Preclinical studies suggest combining CRT with immune checkpoint inhibitors (ICI) may enhance immune responses in E/GEJ cancer. However, the study observed unacceptable toxicity with dual ICI plus CRT, leading to protocol amendments. ➡️ Pathological Response & Biomarker Insights Encouragingly, patients showed substantial pathological responses, especially with nivolumab plus CRT. Baseline PD-L1 expression correlated with response rates and survival outcomes, hinting at potential predictive value. ➡️ ctDNA Dynamics as Predictors Fascinating insights from ctDNA analyses! Detectable ctDNA post-ICI correlated with higher residual tumours, while sustained clearance indicated better outcomes. These findings underscore the evolving landscape of gastro-oesophageal cancer treatment. Integrating immunotherapy demands careful patient selection and toxicity management while highlighting the promise of personalised medicine with biomarker-driven approaches. #PersonalisedMedicine #ClinicalPractice #CancerResearch #TreatmentMonitoring#Biomarkers

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis. A new study in #CancerPathogenesisAndTherapy shows that #immunotherapy with #programmedcelldeath 1 #PD1 inhibitors increases the risk of #InterstitialLungDisease #ILD as compared to #PDL1 inhibitors in patients with #BreastCancer Read more: https://lnkd.in/gF6tin49

Amgen's Imdelltra (tarlatamab) Receives FDA Approval for Lung Cancer Treatment Last week, Amgen's investigational lung cancer immunotherapy, Imdelltra (tarlatamab), has received FDA approval for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) in patients who have progressed after platinum-based chemotherapy. This approval offers a new treatment option for patients with this aggressive form of lung cancer, with clinical trial results showing that Imdelltra shrank tumors in 40% of patients and extended overall survival to a median of 14.3 months, compared to the typical 5 months for this type of cancer. However, Imdelltra comes with a black-box warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). In the DeLLphi-301 trial, 55% of patients experienced CRS, and there was one death from respiratory failure attributed to tarlatamab. Imdelltra has blockbuster potential, with projected 2028 sales at $842 million. This approval marks a significant step forward in lung cancer treatment. https://lnkd.in/ez8mVzKy Image generated using Meta AI #Imdelltra #LungCancerTreatment #FDAApproval #Amgen #MedicalInnovation #CancerResearch #FDA #NewDrug

🎉 Exciting developments in resectable gastro-oesophageal cancer management! 🎉 The phase III CheckMate 577 study unveils FDA-approved adjuvant nivolumab for operable stage II/stage III E/GEJ cancer, marking a paradigm shift. Key points: ➡️ Combining Therapies for Enhanced Responses Preclinical studies suggest combining CRT with immune checkpoint inhibitors (ICI) may enhance immune responses in E/GEJ cancer. However, the study observed unacceptable toxicity with dual ICI plus CRT, leading to protocol amendments. ➡️ Pathological Response & Biomarker Insights Encouragingly, patients showed substantial pathological responses, especially with nivolumab plus CRT. Baseline PD-L1 expression correlated with response rates and survival outcomes, hinting at potential predictive value. ➡️ ctDNA Dynamics as Predictors Fascinating insights from ctDNA analyses! Detectable ctDNA post-ICI correlated with higher residual tumours, while sustained clearance indicated better outcomes. These findings underscore the evolving landscape of gastro-oesophageal cancer treatment. Integrating immunotherapy demands careful patient selection and toxicity management while highlighting the promise of personalised medicine with biomarker-driven approaches. #PersonalisedMedicine #ClinicalPractice #CancerResearch #TreatmentMonitoring#Biomarkers

OUT for #AACR24 : Adagrasib, an irreversible, selective KRASG12C inhibitor, shows promise as a treatment for KRASG12C-mutated colorectal cancer, especially when combined with an anti-EGFR antibody like cetuximab. In the KRYSTAL-1 trial analysis, previously treated patients with KRASG12C-mutated unresectable or metastatic colorectal cancer receiving adagrasib plus cetuximab demonstrated a 34.0% objective response rate (ORR), an 85.1% disease control rate, and a median duration of response of 5.8 months. Median progression-free survival was 6.9 months, and median overall survival was 15.9 months, with manageable treatment-related adverse events. These findings support the potential establishment of a new standard of care and underscore the importance of testing for and identifying KRASG12C mutations in colorectal cancer patients. Source CANCER DISCOVERY (Link to article in comments) Nataliya Uboha Meredith Sellers Pelster, MD, MSCI Tanios Bekaii-Saab Minal Barve Joel Saltzman MD, FASCO Joshua Sabari Pasi Jänne Kenna Anderes PhD, RAC Xiaoyong Yang Hirak Der-Torossian MD MPH Samuel Klempner Scott Kopetz