Pharmaceutical Business Review International’s Post

🟥🟧 The FDA has granted approval for the use of pembrolizumab as neoadjuvant and adjuvant therapy in resectable non-small cell lung cancer. ✅ Yesterday, on 16th of October, the United States Food and Drug Administration (FDA) has approved the use of pembrolizumab (Keytruda, Merck) in combination with platinum-containing chemotherapy as neoadjuvant therapy, followed by single-agent pembrolizumab as post-surgical adjuvant treatment for resectable non-small cell lung cancer (NSCLC) with tumors of at least 4 cm in size or nodes that test positive. 🔶 This treatment involves giving pembrolizumab and chemotherapy before surgery and continuing with pembrolizumab after surgery. It's for patients with a particular size of tumors or positive lymph nodes. ✅ To help get this important information out quickly, the Cancer Discovery Network will share details provided by the FDA, including a link to a document that explains how the drug is used, who it's for, the right dose, and its safety information. 🔴 It's important to know that we are not saying whether the treatment is safe or works; we are just sharing the FDA's information. 🔶 The approval was based on a study called KEYNOTE-671. In this study, 797 patients with a certain stage of lung cancer were given either pembrolizumab or a placebo and chemotherapy before surgery. After surgery, they continued with pembrolizumab or a placebo. You can find more information about the chemotherapy and surgery in the linked document. 🔶 The study looked at how long people lived (overall survival) and how long they lived without their cancer coming back (event-free survival). Those who got pembrolizumab lived longer, and their cancer took longer to come back compared to those who got a placebo. 🔴 Some side effects like nausea and fatigue were seen in patients who received pembrolizumab. Some of them couldn't have surgery because of these side effects, and a few had delays in their surgery. You can learn more about safety in the document linked. ℹ If a doctor prescribes pembrolizumab, the recommended dose is either 200 mg every 3 weeks or 400 mg every 6 weeks, usually given before chemotherapy if it's on the same day. 🔗 Link of the news: https://lnkd.in/gxa2q_ch 🔗 Datasheet of pembrolizumab: https://lnkd.in/gDbTpGvh #FDAApproval #Pembrolizumab #LungCancerTreatment #MedicalBreakthrough #CancerResearch #KEYNOTE671Trial #LungCancerAwareness #InnovativeTherapies #PatientCare

𝐍𝐨𝐯𝐚𝐫𝐭𝐢𝐬 𝐫𝐚𝐝𝐢𝐨𝐥𝐢𝐠𝐚𝐧𝐝 𝐭𝐡𝐞𝐫𝐚𝐩𝐲 𝐋𝐮𝐭𝐚𝐭𝐡𝐞𝐫𝐚® 𝐝𝐞𝐦𝐨𝐧𝐬𝐭𝐫𝐚𝐭𝐞𝐝 𝐬𝐭𝐚𝐭𝐢𝐬𝐭𝐢𝐜𝐚𝐥𝐥𝐲 𝐬𝐢𝐠𝐧𝐢𝐟𝐢𝐜𝐚𝐧𝐭 𝐚𝐧𝐝 𝐜𝐥𝐢𝐧𝐢𝐜𝐚𝐥𝐥𝐲 𝐦𝐞𝐚𝐧𝐢𝐧𝐠𝐟𝐮𝐥 𝐩𝐫𝐨𝐠𝐫𝐞𝐬𝐬𝐢𝐨𝐧-𝐟𝐫𝐞𝐞 𝐬𝐮𝐫𝐯𝐢𝐯𝐚𝐥 𝐢𝐧 𝐟𝐢𝐫𝐬𝐭 𝐥𝐢𝐧𝐞 𝐚𝐝𝐯𝐚𝐧𝐜𝐞𝐝 𝐠𝐚𝐬𝐭𝐫𝐨𝐞𝐧𝐭𝐞𝐫𝐨𝐩𝐚𝐧𝐜𝐫𝐞𝐚𝐭𝐢𝐜 𝐧𝐞𝐮𝐫𝐨𝐞𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐞 𝐭𝐮𝐦𝐨𝐫𝐬 (𝐆𝐄𝐏-𝐍𝐄𝐓𝐬) Novartis Novartis announced the Phase III NETTER-2 trial with Lutathera® (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) met its primary endpoint. First line treatment with Lutathera in combination with long-acting octreotide demonstrated a significant improvement in progression-free survival (PFS) in patients with newly diagnosed somatostatin receptor (SSTR)-positive, Grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) versus high-dose long-acting octreotide alone1,2. No new or unexpected safety findings were observed in the study and data are consistent with the already well-established safety profile of Lutathera1-4. NETs are a type of cancer that originate in neuroendocrine cells throughout the body and are commonly considered slow-growing malignancies. However, some NETs are associated with rapid progression and poor prognosis and in many cases, diagnosis is delayed until patients have advanced disease5-7. Even though NETs are a rare (orphan) disease, their incidence has grown over 500% in the last three decades5-8 and there is an urgent need for additional treatment options for patients newly diagnosed with inoperable or advanced disease. With these results, NETTER-2 is Lutathera’s second Phase III trial showing clinically meaningful results for patients2,4. The approval of Lutathera was originally based on the pivotal NETTER-1 trial, which demonstrated highly significant and clinically meaningful PFS prolongation for patients treated with Lutathera in combination with long-acting octreotide versus high-dose (60 mg) long-acting octreotide for SSTR-positive, inoperable midgut neuroendocrine tumors (NETs) who were progressing despite standard treatment3-4,9. “These positive results for Lutathera are quite remarkable and they represent the potential for radioligand therapy to make a meaningful impact for newly diagnosed patients living with advanced GEP-NETs,” said Jeff Legos Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. “Exploring the use of radioligand therapies in earlier lines of treatment for patients with cancer is part of our larger, collaborative effort to precisely deliver novel treatment modalities directly to the cancer cells to improve patient outcomes.” The findings from NETTER-2 will be presented at an upcoming medical meeting and discussed with regulatory authorities. #patient #clinicaltrials #medical #treatment #cancer #raredisease #neuroendocrine

I'm thrilled to share our recent study, "PD1 Ligand Functionality: A Biomarker of Response to Anti-PD1 Treatment in Patients with HNSCC" now published in NPJ Precision Oncology. In this work, we delve deeper into the potential of PD-1 ligand functionality as a biomarker, aiming to change how we predict response to anti-PD-1 immunotherapy in HNSCC patients. Building upon our previous work, where we established the immune-checkpoint artificial reporter overexpressing PD1 (IcAR-PD1) system, this study underscores that the functionality of PD-1 ligands, beyond mere expression levels, offers a more precise predictor of treatment response. Key Highlights: - Our study, conducted in collaboration with Rambam Health Care Campus, focused on HNSCC patients from various treatment lines with different CPS statuses and response statuses. - We introduced IcAR-PD1 to quantify the functionality of PD-L1 and PD-L2. - Our findings revealed significantly elevated PD-1 ligand scores among responders compared to non-responders to anti-PD-1 therapy. - Notably, our innovative biomarker surpassed the conventional PD-L1 expression biomarker (CPS) in predicting treatment response. - Responders with CPS > 1 exhibited significantly higher levels of functional PD-L2 compared to non-responders. - Responders also demonstrated higher IcAR-PD1 scores regardless of their treatment line. - Although not statistically significant, functional PD-L2 tended to be higher in HNSCC patients receiving anti-PD1 treatment as a first line. While PD-L1 expression has served as the standard biomarker, our research illuminates that the functionality of PD-1 ligands, beyond mere expression levels, offers a more precise predictor of treatment response. Notably, our study underscores the importance of evaluating both PD-L1 and PD-L2 functionality, as they play complementary roles in modulating immune responses. The findings of this research have the potential to refine patient stratification and inform treatment decisions for anti-PD-1 immunotherapy, not only in head and neck cancer but also across other malignancies. I also wish to extend my gratitude to our esteemed partners at Rambam Health Care Campus: Dr. Tarek Taha, Dr. Kamel Mhameed, Dr. Yaniv Zohar and Prof. Salem Billan. Additionally, I want to express my appreciation to the Ben-Gurion University of the Negev team: Orli Abramov, Dr. Ofir Cohen and my mentors, Prof. Moshe Elkabets and Prof. Angel Porgador @n https://lnkd.in/dt8PtRiY

Novartis today presents positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. Scemblix® (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib). Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs. “Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs,” said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). “When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals.” “Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation.” “CML is a chronic condition and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching,” said Gerald Clements, CML caregiver, patient advocate and Steering Committee Treasurer at CML Advocates Network. “Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start.”  #CML #asciminib #Scemblix #Novartis #reimaginemedicine

Interesting in Lancet Oncology: Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study https://lnkd.in/ep_ydAyn Methods In this open-label, phase 2, basket study done in 29 centres in Asia, Europe, and North America, we investigated trastuzumab deruxtecan (5·4 mg/kg every 3 weeks by intravenous infusion) in patients aged 18 years or older with unresectable or metastatic solid tumours with specific activating HER2 mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and disease progression following previous treatment (previous HER2-targeted therapy was permitted) or with no satisfactory alternative treatment options. The primary endpoint was confirmed objective response rate by independent central review. Anti-tumour activity and safety were analysed in all patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT04639219, and is active but no longer recruiting. Findings Between Dec 30, 2020, and Jan 25, 2023, 102 patients (62 [61%] female and 40 [39%] male; median age 66·5 years [IQR 58–72]; 51 [50%] White, two [2%] Black or African American, 38 [37%] Asian, and 11 [11%] did not have race information reported) with solid tumours with activating HER2 mutations received trastuzumab deruxtecan and were included in the anti-tumour activity and safety analyses sets. Patients had a median of three (IQR 2–4) previous treatment regimens. The median duration of follow-up was 8·61 months (IQR 3·71–12·68). The objective response rate by independent central review was 29·4% (95% CI 20·8–39·3; 30 of 102 patients). 52 (51%) patients had a treatment-emergent adverse event of grade 3 or worse; the most common events (in ≥5% of patients) were anaemia (16 [16%]) and neutrophil count decreased (eight [8%]). Drug-related treatment-emergent serious adverse events occurred in ten (10%) patients. Adjudicated drug-related interstitial lung disease or pneumonitis of any grade occurred in 11 patients (11%; three grade 1, five grade 2, one grade 3, and two grade 5); there were two (2%) cases of fatal adjudicated drug-related interstitial lung disease or pneumonitis. Interpretation Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations, with no new safety signals. Prespecified HER2 mutations might be targeted by HER2-directed antibody–drug conjugates and our findings support further investigation of trastuzumab deruxtecan in the pan-tumour setting.

✨Hydrogen-rich water helps improve liver function in colorectal cancer patients treated with mFOLFOX6 chemotherapy.✨ 👉Colorectal cancer patients undergoing mFOLFOX6 chemotherapy may experience adverse effects on liver function. The harmful effects of mFOLFOX6 chemotherapy on liver function are primarily indicated by increased levels of ALT, AST, and BIL.I. Hydrogen-rich water has been studied for its potential to improve liver function in colorectal cancer patients undergoing mFOLFOX6 chemotherapy. 👵 A total of 136 patients aged 41 to 86 participated in the study and were divided into two groups: ▪️ Hydrogen-rich water group (76 patients): Patients in this group started consuming Hydrogen-rich water one day before chemotherapy and continued until the end of the process, totaling 4 days. They consumed 1000 ml of Hydrogen-rich water daily, divided into four doses of 250 ml each. Hydro-rich water was consumed 0.5 hours after meals and before bedtime. Patients continuously consumed Hydrogen-rich water throughout the entire chemotherapy process. ▪️ Placebo group (60 patients): Patients in this group consumed distilled water with a daily amount of 1000 ml, divided into four doses of 250 ml each. 👉 The study found that there were no statistically significant differences in the levels of ALT, AST, and BIL.I before and after chemotherapy in the Hydrogen-rich water group. However, there were significant differences in the levels of these liver function markers before and after chemotherapy in the placebo group. The probability and degree of chemotherapy-induced liver damage were lower in the Hydro-rich water group compared to the placebo group. Specifically: 1️⃣ ALT (Alanine Aminotransferase) levels before and after chemotherapy: Hydrogen-rich water group: 28.72±1.6 → 31.28±1.47 (IU/l) Placebo group: 26.78±3.8 → 58.22±2.46 (IU/l) 2️⃣ AST (Aspartate Transaminase) levels before and after chemotherapy: Hydrogen-rich water group: 22.74±2.74 → 23.43±2.66 (IU/l) Placebo group: 23.43±3.24 → 39.28±5.17 (IU/l) 3️⃣ BIL.I (Indirect Bilirubin) levels before and after chemotherapy: Hydrogen-rich water group: 11.70±1.02 → 14.20±1.449 (µmol/l) Placebo group: 10.98±3.17 → 20.70±3.07 (µmol/l) 🔬 The current study shows that colorectal cancer patients treated with Hydrogen-rich water alongside mFOLFOX6 chemotherapy did not exhibit significant differences in liver function markers (ALT, AST, and BIL.I) after treatment. This suggests that Hydrogen-rich has a protective effect on liver function in these patients. https://lnkd.in/gudY7MSb or you can or contact Kim Long Phat via: Email: infokimlongphatcorp@gmail.com Hotline: 0888 214 839 - 02822 170 839 #LourdesHydrofix #KimLongPhat #H2Factory #Hydrogenwater #Vietnam #Asia #Japan #HydrogenInhalation #SmartwaterSolution

AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in the European Union (EU) for the 1st-line treatment of adult patients with advanced epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the FLAURA2 Phase III trial published in The New England Journal of Medicine. In the trial, Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38% by investigator assessment compared to Tagrisso monotherapy, which is the 1st-line global standard of care (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Median progression-free survival (PFS) was 25.5 months for patients treated with Tagrisso plus chemotherapy, an 8.8-month improvement versus Tagrisso monotherapy (16.7 months). PFS results from blinded independent central review (BICR) were consistent with the results by investigator assessment, showing 29.4 months median PFS with Tagrisso plus chemotherapy, a 9.5-month improvement over Tagrisso monotherapy (19.9 months) (HR 0.62; 95% CI 0.48-0.80; nominal p=0.0002). Results from a prespecified exploratory analysis of patients in the FLAURA2 trial with brain metastases at baseline showed Tagrisso plus chemotherapy reduced the risk of central nervous system (CNS) disease progression or death by 42% compared to Tagrisso monotherapy (HR 0.58; 95% CI 0.33-1.01) as assessed by BICR. With two years of follow up, 74% of patients treated with Tagrisso plus chemotherapy had not experienced CNS disease progression or death versus 54% of patients treated with Tagrisso monotherapy. David Planchard, MD, PhD, Thoracic Oncologist at Gustave Roussy Institute of Oncology and principal investigator for the trial, said: “Today’s news marks a significant advance for patients with EGFR-mutated lung cancer in Europe, providing a new 1st-line treatment option with osimertinib now in combination with chemotherapy. The FLAURA2 results build on the established efficacy of osimertinib monotherapy, showing a meaningful nine-month improvement in progression-free survival and offering physicians the option to tailor treatment to a patient’s specific needs.” David Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “This approval reinforces Tagrisso as the backbone therapy in EGFR-mutated lung cancer either as monotherapy or in combination with chemotherapy. This is especially important for those with more aggressive disease, including patients whose cancer has spread to the brain and those with L858R mutations.” #Oncology #LungCancer #NSCLC #Osimertinib #Tagrisso #AstraZeneca #WhatScienceCanDo

Exploring China's Indigenous Drug Anlotinib: A Beacon of Hope for Digestive Tract Tumor Patients In the continuous advancement of medicine, Anlotinib combined chemotherapy is emerging as a frontline therapy for advanced, unresectable liver metastases from digestive tract tumors. Let's delve into the latest findings from a phase II clinical trial initiated by researchers from the Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital. ALTER-G-001 Cohort C: A Glimmer of Hope As of November 13, 2023, a total of 41 patients were enrolled in ALTER-G-001 Cohort C, comprising mainly 29 cases of pancreatic cancer, 6 cases of gastric cancer, and 5 cases of biliary tract cancer. These patients had a median age of 64 years, with 63.4% being male, and 92.7% having an ECOG performance status of 1. 56.1% of patients had liver metastases only. All patients received Anlotinib combined with standard chemotherapy. The efficacy assessment revealed partial responses in 16 patients and stable disease (with tumor shrinkage in 14 patients) in 17 patients, resulting in an objective response rate (ORR) of 42.1% and a disease control rate (DCR) of 86.8%. Among evaluable pancreatic cancer patients, the ORR and DCR were 42.3% and 88.5%, respectively. These data underscore the significant efficacy of Anlotinib in treating digestive tract tumors. Safety and Tolerability Regarding safety, 39 patients experienced treatment-related adverse events (TEAEs), with 53.7% of patients experiencing ≥Grade 3 TEAEs. Major adverse events included neutropenia (19.5%), leukopenia (14.6%), and thrombocytopenia (9.8%). However, despite some adverse events, the overall safety profile of Anlotinib combined chemotherapy remains acceptable. Looking Ahead Anlotinib, developed independently by the Chinese pharmaceutical company CTTQ PHARMA, is changing the treatment landscape for patients with advanced liver metastases from digestive tract tumors. Apart from pancreatic cancer, Anlotinib is undergoing clinical trials for various cancers, including non-small cell lung cancer, soft tissue sarcoma, gastric cancer, colorectal cancer, medullary thyroid carcinoma, differentiated thyroid carcinoma, and esophageal squamous cell carcinoma. This brings more hope and options for patients. Conclusion Anlotinib combined chemotherapy as a frontline treatment demonstrates good efficacy and acceptable safety for patients with advanced liver metastases from digestive tract tumors, bringing a ray of hope. We look forward to further research on this therapy and more patients benefiting from it in the future. May every patient find healing and hope in the progress of medicine. We have access to medical resources from all cancer hospitals in China and can assist patients in receiving treatment from the best and top-tier oncologists in the CHINA. doctor.huang@globecancer.com WhatsApp：+8613717959070 #Anlotinib #DigestiveTractTumors #CancerTreatment #MedicalAdvancements

The FDA granted an accelerated approval for Enhertu to treat adults with unresectable or metastatic HER2-positive solid tumors. The approval makes Enhertu the first FDA approved tumor-agnostic HER2-directed ADC and clears the drug for use in patients who’ve already received primary systemic treatment and have no other satisfactory alternatives Efficacy was evaluated in 192 adult patients with previously treated unresectable or metastatic HER2-positive (IHC 3+) solid tumors who were enrolled in one of three multicenter trials: DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831). All three trials excluded patients with a history of interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids or ILD/pneumonitis at screening and clinically significant cardiac disease. Patients were also excluded for active brain metastases or ECOG performance status >1. Treatment was administered until disease progression, death, withdrawal of consent, or unacceptable toxicity. The major efficacy outcome measure in all three trials was confirmed objective response rate (ORR), and an additional efficacy outcome was duration of response (DOR). All outcomes were assessed by independent central review (ICR) based on RECIST v1.1. In DESTINY-PanTumor02, ORR was 51.4% (95% CI: 41.7, 61.0) and median DOR was 19.4 months (range 1.3, 27.9+). In DESTINY-Lung01, ORR was 52.9% (95% CI: 27.8, 77.0) and median DOR was 6.9 months (range 4.0, 11.7+). In DESTINY-CRC02, ORR was 46.9% (95% CI: 34.3, 59.8), and DOR was 5.5 months (range 1.3+, 9.7+). The most common adverse reactions (≥20%), including laboratory abnormalities, were decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, fatigue, decreased lymphocyte count, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, decreased appetite, alopecia, diarrhea, decreased blood potassium, constipation, decreased sodium, stomatitis, and upper respiratory tract infection. The prescribing information includes a Boxed Warning advising health professionals of the risk of interstitial lung disease and embryo-fetal toxicity. At the time, Daiichi said it expected Enhertu sales to clock in at 383.9 billion Japanese yen (about $2.6 billion) for the 12 months ending March 31, including profits from regions where AZ books sales of the ADC. Along with that boosted global forecast, Daiichi reduced its 12-month sales projection in the U.S. by $30 million to $1.58 billion. The news: https://lnkd.in/gttvMR3W FDA release: https://lnkd.in/gQfb-t3Y