A Phase II Single-Center Exploratory Study on the Efficacy and Safety of Neoadjuvant Chemotherapy Sequentially Combined with Sintilimab in Resectable EGFR-Mutant Stage II-IIIB Non-Squamous Non-Small Cell Lung Cancer Patients

This study is a prospective, single-arm, single-center Phase II trial, aiming to investigate efficacy and safety of neoadjuvant chemotherapy sequentially combined with sintilimab in resectable EGFR-mutant stage II-IIIB non-squamous NSCLC patients

Start Date31 Mar 2025

Sponsor / Collaborator

Shanghai Chest Hospital

ChiCTR2400089107 / SuspendedPhase 4IIT

The Effectiveness and Safety of Sintilimab Plus Bevacizumab Combined with Pemetrexed and Platinum-Based Drugs in Retrospective Analysis for Advanced Non-Small Cell Lung Cancer Patients Without Targeted Therapy

Start Date01 Oct 2024

Sponsor / Collaborator

Anhui Chest Hospital

NCT06576635 / Not yet recruitingNot ApplicableIIT

LUNG-05: Investigating Chemotherapy Effectiveness for NSCLC Metastatic Patients

This is a Single arm, Simon's two stage pilot study in which patients with Non-Small Cell Lung Cancer (NSCLC) with metastatic disease 2L and beyond will receive OncoChoice-informed chemotherapy following National Cancer Care Network (NCCN) treatment guidelines on dosage and scheduling for NSCLC FDA approved drugs.

Start Date01 Sep 2024

Sponsor / Collaborator

University of Illinois

100 Clinical Results associated with Pemetrexed Dipotassium

100 Translational Medicine associated with Pemetrexed Dipotassium

100 Patents (Medical) associated with Pemetrexed Dipotassium

276

Literatures (Medical) associated with Pemetrexed Dipotassium

01 Mar 2025·BIOMATERIALS

Biomimetic polymeric nanoreactors with photooxidation-initiated therapies and reinvigoration of antigen-dependent and antigen-free immunity

Article

Author: Yu, Nuo ; Tao, Cheng ; Wen, Mei ; Niu, Shining ; Qiu, Pu ; Zhuang, Zixuan ; Chen, Zhigang

Immune cell-mediated anticancer modalities usually suffer from immune cell exhaustion and limited efficacy in solid tumors. Herein, the oxygen-carrying biomimetic nanoreactors (BNR2(O₂)) have been developed with photooxidation-driven therapies and antigen-dependent/antigen-free immune reinvigoration against xenograft tumors. The BNR2(O₂) composes polymeric nanoreactors camouflaged with cancer cell membranes can efficiently target homotypic tumors. It continuously releases O₂ to boost intracellular reactive oxygen species (ROS) to oxide diselenide bonds, which controllably releases seleninic acids and anti-folate Pemetrexed compared to hydrogen peroxide and glutathione incubation. The O₂-rich microenvironment sensitizes Pemetrexed and blocks programmed cell-death ligand 1 (PD-L1) to reverse T cell immunosuppression. The ROS and Pemetrexed upregulate pro-apoptosis proteins and inhibit folate-related enzymes, which cause significant apoptosis and immunogenic cell death to stimulate dendritic cell maturation for improved secretion of cytokines, expanding antigen-dependent T cell immunity. Furthermore, by regulating the release of seleninic acids, the checkpoint receptor human leukocyte antigen E of tumor cells can be blocked to reinvigorate antigen-free natural killer cell immunity. This work offers an advanced antitumor strategy by bridging biomimetic nanoreactors and modulation of multiple immune cells.

01 Jan 2025·COLLOIDS AND SURFACES B-BIOINTERFACES

Pemetrexed-loaded supramolecular acetal-functionalized pH-responsive nanocarriers selectively induce apoptosis through biotin receptors to enhance antitumor efficacy

Article

Author: Bakshi, Avijit Kumar ; Kumar, Ankit ; Shukla, Ravi Prakash ; Rai, Nikhil ; Sharma, Madhu ; Singh, Neha ; Mishra, Prabhat Ranjan ; Gautam, Shalini ; Marwaha, Disha ; kumar, Ankit ; Agarwal, Neha ; Tiwari, Pratiksha

A novel pH-responsive crystalsomes has been developed using acetal-functionalized pillar[5]arenes (AP[5]) and methyl viologen (MV) through host-guest interactions. The successful synthesis of AP[5] was confirmed via ¹H-NMR spectroscopy, while the formation of the host-guest complex between AP[5] and MV was also verified using ¹H-NMR. The supramolecular assemblies formed at a 1:1 molar ratio of AP[5] to MV exhibited remarkable colloidal stability, a negative surface charge, and a high association constant.An acetal-functionalized pillara[5]arenes (AP[5]) crystalsomes were fabricated to reduce the toxicity of pemetrexed (PMX) in off-target sites and deliver the therapeutic doses to the active sites. Extensive characterization of the crystalsomes was performed, revealing their morphology and crystalline structure through SEM and TEM imaging. WAXS analysis confirmed the crystalline nature of the assemblies, and SAED patterns indicated that the crystalsome shell consisted of lamellae resembling single crystals with polymer chains oriented parallel to the interface. To enhnace the targeting capabilities, the surface of the crystalsomes was modified with biotin by conjugating viologen with biotin (MV-BT), aiming to target biotin receptors overexpressed on tumor cells. These biotin -modified crystalsomes (PMX-BT@CLs) were designed to be acid-labile facilitating the release of encapsulated drugs upon cellular internalization, as confirmed by confocal laser scanning microscopy (CLSM). In vivo, studies demonstrated that the PMX-loaded crystalsomes remained in circulation for extended period, showing improved pharmacokinetics. The area under the curve (AUC) of PMX-BT@CLs was approxiately 3.9 times higher than that of the free drug. Additionally, the relative tumor volume was found to be about 3.5 times lower in the group treated with biotin-modified crystalsomes compared to those treated with free PMX. The mean survival time was also significantly enhanced in the PMX-BT@CLs group. This study underscores the potential of using host-guest motifs in drug delivery app;ications, demonstrating the PMX can effectively targted to tumor sites with minimal off-target toxicity.

01 Dec 2024·CANCER CHEMOTHERAPY AND PHARMACOLOGY

A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed

Article

Author: Boosman, R J ; Hilbrands, L B ; Schulte, J ; Ter Heine, R ; Derijks, H J ; Beunders, R ; van den Heuvel, M M ; Burger, D M ; de Rouw, N ; Pickkers, P ; Hartmann, O

Abstract:

Introduction:

For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal. Therefore, the aim of this study was to investigate the performance of the kidney function biomarkers serum creatinine, cystatin C and pro-enkephalin in terms of predicting the elimination of pemetrexed.

Methods:

We performed a population pharmacokinetic analysis using a dataset from two clinical trials containing pharmacokinetic data of pemetrexed and measurements of all three biomarkers. A three-compartment model without covariates was fitted to the data and the obtained individual empirical Bayes estimates for pemetrexed clearance were considered the “true” values (Cltrue). Subsequently, the following algorithms were tested as covariates for pemetrexed clearance: the Chronic Kidney Disease Epidemiology Collaboration equation using creatinine (CKD-EPICR), cystatin C (CKD-EPICYS), a combination of both (CKD-EPICR-CYS), pro-enkephalin as an absolute value or in a combined algorithm with age and serum creatinine, and lastly, a combination of pro-enkephalin with cystatin C.

Results:

The dataset consisted of 66 subjects with paired observations for all three kidney function biomarkers. Inclusion of CKD-EPICR-CYS as a covariate on pemetrexed clearance resulted in the best model fit, with the largest decrease in objective function (p < 0.00001) and explaining 35% of the total inter-individual variability in clearance. The predictive performance of the model to containing CKD-EPICR-CYS to predict pemetrexed clearance was good with a normalized root mean squared error and mean prediction error of 19.9% and 1.2%, respectively.

Conclusions:

In conclusion, this study showed that the combined CKD-EPICR-CYS performs best in terms predicting pharmacokinetics of pemetrexed. Despite the hypothesized disadvantages, creatinine remains to be a suitable and readily available marker to predict pemetrexed clearance in clinical practice.

News (Medical) associated with Pemetrexed Dipotassium

08 Sep 2024

·www.businesswire.com

Novel computational pathology-based TROP2 biomarker for datopotamab deruxtecan was predictive of clinical outcomes in patients with non-small cell lung cancer in TROPION-Lung01 Phase III trial

WILMINGTON, Del.--( BUSINESS WIRE )--Results from an exploratory analysis of the TROPION-Lung01 Phase III trial showed TROP2 as measured by AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who were treated with datopotamab deruxtecan (Dato-DXd). In patients with TROP2-QCS biomarker positive tumors, datopotamab deruxtecan demonstrated a meaningfully greater magnitude of efficacy versus docetaxel than in the overall trial population. These results will be featured in a Presidential Symposium ( PL02.11 ) at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer. TROP2 is a protein broadly expressed in NSCLC on the surface of and inside tumor cells. 1,2 When assessed using conventional immunohistochemistry (IHC)-based pathology, TROP2 expression has not been predictive of patient responses to TROP2-directed antibody drug conjugates (ADC). 3,4 QCS is a fully supervised computational pathology platform, developed by AstraZeneca, that analyzes digitized images of patient tissue samples and precisely quantifies targets, like TROP2, on and inside a tumor cell. Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo. In this analysis, QCS was used to analyze tissue samples collected from patients in TROPION-Lung01. This produced a normalized membrane ratio for each tumor cell in each sample. Patients’ tumors were considered TROP2-QCS biomarker positive if the majority (≥75%) of tumor cells exhibited a ratio below a predetermined value (≤0.56), indicating a greater proportion of TROP2 in the cytoplasm. The analysis showed a greater proportion of patients with nonsquamous NSCLC were considered TROP2-QCS biomarker positive than those with squamous NSCLC (66% vs. 44%, respectively). The threshold for biomarker positivity was optimized for progression-free survival (PFS) in the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations because it represents a population with significant unmet medical need and without actionable biomarkers. In patients with TROP2-QCS biomarker positive tumors (60% of the biomarker evaluable population including patients with nonsquamous and squamous NSCLC), datopotamab deruxtecan reduced the risk of disease progression or death by 43% versus docetaxel (median PFS of 6.9 vs. 4.1 months; hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.41-0.79). By comparison, in the primary analysis of the overall trial population, datopotamab deruxtecan reduced the risk of disease progression or death by 25% versus docetaxel (PFS of 4.4 vs. 3.7 months; HR 0.75; 95% CI 0.62-0.91; p=0.004) as presented at the 2023 European Society for Medical Oncology Congress. 5 In the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations and with TROP2-QCS biomarker positive tumors, datopotamab deruxtecan reduced the risk of disease progression or death by 48% (PFS of 7.2 vs. 4.1 months; HR 0.52; 95% CI 0.35-0.78). Marina Garassino, MD, The University of Chicago, Professor of Medicine and investigator in the trial, said: “ TROP2 is broadly expressed on solid tumor cells, including non-small cell lung cancer, but it has yet to be established as a predictive biomarker for any TROP2-directed antibody drug conjugate. We have shown with this analysis that the more precise quantitative measurement of TROP2 on and inside tumor cells, enabled by AstraZeneca’s computational pathology platform, can identify which patients with non-small cell lung cancer are most likely to benefit from treatment with datopotamab deruxtecan.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ This analysis demonstrates the power of our computational pathology platform to discover new predictive biomarkers and substantially improve patient selection for datopotamab deruxtecan. It also has great potential to help more precisely select patients across our broader antibody drug conjugate portfolio. We are excited to extend our collaboration with Roche Tissue Diagnostics with the aim of validating this exploratory approach for TROP2, developing the companion diagnostic and bringing it to the clinic as quickly as possible.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “ The results from the QCS analysis support the potential of TROP2, as measured by quantitative continuous scoring, as a predictive biomarker for datopotamab deruxtecan and begin to answer the question of why certain patients with non-small cell lung cancer respond better to treatment. These insights are critical to advancing our understanding of how we can more precisely identify patients with non-small cell lung cancer who may benefit from treatment with our TROP2-directed antibody drug conjugate.” In the biomarker evaluable population, no new safety concerns were identified and rates of Grade 3 or higher treatment-related adverse events (TRAE) were similar regardless of TROP2 status. In patients with TROP2-QCS biomarker positive tumors, Grade 3 or higher TRAEs occurred in 30% and 46% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common Grade 3 or higher TRAEs were stomatitis (7%, 3%) and ocular surface events (3%, 0%). Grade 3 or higher adjudicated drug-related interstitial lung disease events occurred in 3% and 1% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. Summary of TROPION-Lung01 QCS analysis results Overall biomarker evaluable population (n=352) TROP2-QCS biomarker positive TROP2-QCS biomarker negative Dato-DXd (n=107) Docetaxel (n=107) Dato-DXd (n=65) Docetaxel (n=73) Median PFS 6.9 months 4.1 months 2.9 months 4.0 months HR (95% CI) 0.57 (0.41-0.79) 1.16 (0.79-1.70) ORR 32.7% 10.3% 16.9% 15.1% Nonsquamous histology without actionable genomic alterations subgroup (n=221) Dato-DXd (n=68) Docetaxel (n=72) Dato-DXd (n=40) Docetaxel (n=41) Median PFS 7.2 months 4.1 months 4.0 months 4.4 months HR (95% CI) 0.52 (0.35-0.78) 1.22 (0.74-2.00) ORR 36.8% 15.3% 22.5% 12.2% CI, confidence interval; HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival AstraZeneca and Roche Tissue Diagnostics collaborate to co-develop and commercialize the TROP2-QCS biomarker companion diagnostic AstraZeneca and Roche Tissue Diagnostics are extending their existing collaboration to co-develop a novel companion diagnostic incorporating AstraZeneca’s proprietary computational pathology platform, QCS, which will be deployed within Roche's navify ® Digital Pathology image management system. Jill German, Head, Roche Tissue Diagnostics, said: “ Our collaboration with AstraZeneca continues to push the boundaries of traditional cancer diagnostics. By developing an innovative Al tool that goes beyond human capabilities, the solution will be able to help determine which cancer patients are most likely to benefit from targeted therapies, potentially improving patient care.” Under this expanded collaboration, Roche Tissue Diagnostics and AstraZeneca will co-develop and commercialize a novel companion diagnostic in Roche’s navify ® Digital Pathology platform, based on the QCS computational pathology platform, to aid pathologists in interpreting an investigational VENTANA TROP2 assay. As the leading provider of pathology lab solutions, Roche Tissue Diagnostics is delivering an end-to-end digital pathology workflow from tissue staining to producing high-quality digital images that can be reliably assessed using automated clinical image analysis algorithms. Notes Advanced non-small cell lung cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 6 NSCLC is the most common type of lung cancer, accounting for about 80% of cases. 7 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively. 8 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy. 9-11 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects. 9-11 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 1 There is currently no TROP2-directed ADC approved for the treatment of lung cancer. 12,13 TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m 2 ) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. The program includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and datopotamab deruxtecan in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References Mito R, et al . Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int . 2020;70(5):287-294. Shvartsur A, et al . Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes & Cancer . 2015 Mar;6(3-4): 84-105. Shimizu T, et al. J Clin Oncol 2023;41:4678-87. Heist RS, et al. J Clin Oncol . 2017;35:2790-7. Ahn M-J, et al . Datopotamab deruxtecan (Dato-DXd) vs doxetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): results of the randomized phase 3 study TROPION-Lung01. Presented at: ESMO Congress 2023, 20-24 October 2023; Madrid, Spain. LBA12. World Health Organization. Global Cancer Observatory: Lung. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed September 2024. Cancer.net. Lung Cancer – Non-Small Cell: Statistics. Available at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer . Accessed September 2024. National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, 1975-2017 . Accessed September 2024. Chen R, et al . Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol . 2020;13(1):58. Majeed U, et al . Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol . 2021;14(1):108. Pircher, A, et al . Docetaxel in the Treatment of Non-small Cell Lung Cancer (NSCLC) – An Observational Study Focusing on Symptom Improvement. Anticancer Research . 2013;33(9):3831-3836. Rodríguez-Abreau D, et al . Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Ann Onc . 2021 Jul;32(7): 881-895. American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html. Accessed September 2024. US-93494 Last Updated 9/24

Phase 3Clinical ResultLicense out/in

12 Aug 2024

·www.globenewswire.com

Junshi Biosciences Announces Acceptance of Supplemental New Drug Application for Toripalimab as First-Line Treatment of Unresectable/Metastatic Melanoma

SHANGHAI, Aug. 12, 2024 (GLOBE NEWSWIRE) -- Shanghai Junshi Biosciences Co., Ltd (Junshi Biosciences, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced that the National Medical Products Administration (NMPA) has accepted for review the supplemental new drug application (sNDA) for toripalimab (trade name: TUOYI®, product code: JS001) for the first-line treatment of unresectable or metastatic melanoma. Melanoma is the most malignant type of skin cancer. According to the 2022 GLOBOCAN Report, approximately 332,000 new melanoma cases and approximately 59,000 deaths were recorded globally that year. Though melanoma is relatively uncommon in China, its mortality rate is high (5,000 deaths amongst approximately 9,000 new cases in 2022) and its incidence rate is rising year by year. So far, anti-PD-1 monoclonal antibodies have only been approved for the second-line or beyond treatment of advanced melanoma in China, however, the first-line standard treatment of advanced melanoma is still dominated by traditional chemotherapy or targeted therapy (limited to patients with BRAF V600 mutation). Therefore, there is an urgent clinical need for first-line immunotherapy options for patients with advanced melanoma in China. The sNDA is mainly based on the MELATORCH study (NCT03430297), a multi-center, randomized, open-label, positive-controlled Phase III clinical study. It is China’s first and only pivotal registrational clinical study of a PD-(L)1 inhibitor as a first-line treatment for advanced melanoma that has yielded positive results, and was designed to compare the efficacy and safety of toripalimab with dacarbazine for the first-line treatment of systemic treatment-naïve patients with unresectable or metastatic melanoma. The study was led by Principal Investigator Professor Guo Jun from Peking University Cancer Hospital in 11 clinical centers across the country. In September 2023, MELATORCH’s primary endpoint of progression-free survival (“PFS,” based on independent radiological review) met the pre-defined efficacy boundary. The results showed that compared with dacarbazine, toripalimab as the first-line treatment for unresectable or metastatic melanoma significantly prolonged the PFS of patients. The safety profile of toripalimab is comparable to that of prior studies, and no new safety signals were identified. The detailed data of this study will be presented by Junshi Biosciences at an upcoming international academic conference. Principal Investigator and Chairman of CSCO Experts Committee on Malignant Melanoma, Professor Jun GUO from Beijing Cancer Hospital, said, “Within the last 5 years, toripalimab has become the standard therapy for second-line and beyond salvage treatment of advanced melanoma in China, which significantly altered the treatment landscape and offered groundbreaking survival benefits to many Chinese patients. However, we also recognize that treating Chinese melanoma patients presents greater challenges than treating Caucasian melanoma patients. Thus, despite PD-1 inhibitors being approved internationally for first-line treatment of melanoma and even as adjuvant therapy for early-stage patients, no immune checkpoint inhibitor has yet been approved for these indications in China. The acceptance of toripalimab’s sNDA is proof of its value and importance in earlier line treatment. We eagerly anticipate its approval, as it would allow Chinese melanoma patients to benefit from immunotherapy even earlier.” “In 2018, toripalimab made history as the first domestically developed anti-PD-1 monoclonal antibody approved for second-line and beyond treatment of advanced melanoma, leaving its brilliant mark in China’s pharmaceutical and biotech development,” General Manager and CEO of Junshi Biosciences, Dr. Jianjun ZOU, said. “Today, our efforts continue with the NMPA’s acceptance of the 12th sNDA for toripalimab, and toripalimab is poised to become China’s first immunotherapy for melanoma. We will work closely with regulatory authorities to provide better clinical treatments to patients as soon as possible.” About Toripalimab Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells. More than forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types, including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney, and skin. In the Chinese mainland, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI®). Currently, there are eight approved indications for toripalimab in the Chinese mainland: unresectable or metastatic melanoma after failure of standard systemic therapy;recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy;locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC;in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC);in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC);in combination with chemotherapy as perioperative treatment and subsequently with monotherapy as adjuvant therapy for the treatment of adult patients with resectable stage IIIA-IIIB NSCLC;in combination with axitinib for the first-line treatment of patients with medium to high risk unresectable or metastatic renal cell carcinoma (RCC);in combination with etoposide plus platinum for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC);in combination with paclitaxel for injection (albumin-bound) for the first-line treatment of recurrent or metastatic triple-negative breast cancer (TNBC). The first six indications have been included in the National Reimbursement Drug List (NRDL) (2023 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. In April 2024, the Drug Office at the Department of Health in the Government of the Hong Kong Special Administration Region (DO) accepted the NDA for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. In the United States, the US Food and Drug Administration (FDA) has approved the Biologics License Application for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy in October 2023. The FDA has granted toripalimab 2 Breakthrough Therapy designations for the treatment of NPC, 1 Fast Track designation for the treatment of mucosal melanoma, and 5 Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC). In Europe, marketing authorization applications (MAA) were accepted by the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) for 1) toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC, in December 2022 and February 2023. In Australia, the new chemical entity (NCE) application was accepted by the Australia Therapeutic Goods Administration (TGA) in November 2023. The TGA has also granted toripalimab an Orphan Drug designation for the treatment of NPC. In Singapore, the NDA application was accepted by the Singapore Health Sciences Authority (HSA) in January 2024. The HSA has also granted priority review designation for the NDA. About Junshi Biosciences Founded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Four of the company’s innovations have already reached the Chinese or international markets, one of which is toripalimab, China’s first domestically produced and independently developed anti-PD-1 monoclonal antibody, approved in China and the US. Additionally, more than 30 drugs are currently in clinical development. During the COVID-19 pandemic, Junshi Biosciences actively shouldered the social responsibilities of a Chinese pharmaceutical company through its involvement in developing etesevimab, MINDEWEI®, and other novel therapies for the prevention and treatment of COVID-19. With a mission of “providing patients with world-class, trustworthy, affordable, and innovative drugs,” Junshi Biosciences is “In China, For Global.” At present, the company boasts approximately 3,000 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc.). For more information, please visit: http://junshipharma.com. Junshi Biosciences Contact InformationIR Team:Junshi Biosciencesinfo@junshipharma.com+ 86 021-6105 8800 PR Team:Junshi BiosciencesZhi Lizhi_li@junshipharma.com+ 86 021-6105 8800

Orphan DrugBreakthrough TherapyDrug ApprovalPhase 3NDA

29 Jul 2024

·www.businesswire.com

Amneal Receives U.S. FDA Approval for Potassium Phosphates Injection IV Bags

BRIDGEWATER, N.J.--( BUSINESS WIRE )--Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX) (“Amneal” or the “Company”) today announced that it has received New Drug Application (“NDA”) approval from the U.S. Food and Drug Administration (FDA) for its new presentation of potassium phosphates in 0.9% sodium chloride injection intravenous (IV) ready-to-use (RTU) bags. This sterile presentation reduces the compounding steps for clinicians typically required with administering the product. Potassium Phosphates in Sodium Chloride Injection is a phosphorus replacement product indicated as a source of phosphorus to correct hypophosphatemia in adults and pediatric patients who weigh 40 kg or greater when oral or enteral replacement is not possible, insufficient or contraindicated. The product is available as a single-dose infusion bag and is formulated without preservatives. It is natural rubber latex-free and can be stored at room temperature. In 2024, Amneal has already launched PEMRYDI RTU ® , a ready-to-use formulation of pemetrexed, and FOCINVEZ ® , a ready-to-use version of fosaprepitant. Both products offer hospitals and oncology clinics new, value-added presentations that should improve pharmacy efficiency by eliminating preparation steps. The expected third quarter launch of potassium phosphates injection IV bag represents the Company’s third 505(b)(2) launch this year. “We are pleased to offer this new differentiated injectable product to hospitals,” said Andy Boyer, Executive Vice President, Chief Commercial Officer - Generics. “This new IV parenteral infusion bag is preservative-free and can be stored at room temperature. With the addition of new 505(b)(2) injectables, we are meaningfully expanding our injectables portfolio.” "Our third 505(b)(2) injectable product approval this year reflects our deep capabilities in developing new and impactful complex products. We look forward to bringing more innovative 505(b)(2) injectable products to market over the coming years," said Dr. Srinivas Kone, Senior Vice President, Chief Scientific Officer – Generics. Adverse effects reported for the potassium phosphates injection IV bags include hyperkalemia, hyperphosphatemia, hypocalcemia and hypomagnesemia. For full prescribing information, see package insert located here . About Amneal Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX), headquartered in Bridgewater, NJ, is a global pharmaceutical company. We make healthy possible through the development, manufacturing, and distribution of a diverse portfolio of over 280 pharmaceutical products, primarily within the United States. In its Generics segment, the Company is expanding across a broad range of complex product categories and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceuticals focused primarily on central nervous system and endocrine disorders, with a pipeline focused on unmet needs. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more information, please visit www.amneal.com . Cautionary Statement on Forward-Looking Statements Certain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations, financial results, or forecasts for the future, including among other things: discussions of future operations; expected or estimated operating results and financial performance; and statements regarding our positioning, including our ability to drive sustainable long-term growth, and other non-historical statements. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates,” and similar words, or the negatives thereof, are intended to identify estimates and forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These forward-looking statements are based on current expectations of future events, including with respect to future market conditions, company performance and financial results, operational investments, business prospects, new strategies and growth initiatives, the competitive environment, and other events. If the underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of the Company. Such risks and uncertainties include, but are not limited to: our ability to successfully develop, license, acquire and commercialize new products on a timely basis; the competition we face in the pharmaceutical industry from brand and generic drug product companies, and the impact of that competition on our ability to set prices; our ability to obtain exclusive marketing rights for our products; our revenues are derived from the sales of a limited number of products, a substantial portion of which are through a limited number of customers; the impact of a prolonged business interruption within our supply chain; the continuing trend of consolidation of certain customer groups; our dependence on third-party suppliers and distributors for raw materials for our products and certain finished goods; legal, regulatory and legislative efforts by our brand competitors to deter competition from our generic alternatives; our dependence on information technology systems and infrastructure and the potential for cybersecurity incidents; our ability to attract, hire and retain highly skilled personnel; risks related to federal regulation of arrangements between manufacturers of branded and generic products; our reliance on certain licenses to proprietary technologies from time to time; the significant amount of resources we expend on research and development; the risk of claims brought against us by third parties; risks related to changes in the regulatory environment, including U.S. federal and state laws related to healthcare fraud abuse and health information privacy and security and changes in such laws; changes to Food and Drug Administration product approval requirements; the impact of healthcare reform and changes in coverage and reimbursement levels by governmental authorities and other third-party payers; our dependence on third-party agreements for a portion of our product offerings; our substantial amount of indebtedness and our ability to generate sufficient cash to service our indebtedness in the future, and the impact of interest rate fluctuations on such indebtedness; our potential expansion into additional international markets subjecting us to increased regulatory, economic, social and political uncertainties, including recent events affecting the financial services industry; our ability to identify, make and integrate acquisitions or investments in complementary businesses and products on advantageous terms; the impact of global economic, political or other catastrophic events; our obligations under a tax receivable agreement may be significant; and the high concentration of ownership of our class A common stock and the fact that we are controlled by the Amneal Group. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Investors are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof.

Drug Approval

100 Deals associated with Pemetrexed Dipotassium

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Indication	Country/Location	Organization	Date
Locally Advanced Lung Non-Squamous Non-Small Cell Carcinoma	US	Avyxa Pharma	28 Jun 2024
Malignant Pleural Mesothelioma	US	Avyxa Pharma	28 Jun 2024
Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	US	Avyxa Pharma	28 Jun 2024
Non-squamous non-small cell lung cancer	US	Avyxa Pharma	28 Jun 2024
Recurrent Lung Non-Squamous Non-Small Cell Carcinoma	US	Avyxa Pharma	28 Jun 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


WCLC2024 Manual	Not Applicable	Non-squamous non-small cell lung cancer	469	IO monotherapy	wfuhlqmhvq(zeexkikedr) = zufzgzmrmy snoazbpazv (lmjzqhlnnd ) View more	Negative	09 Sep 2024
WCLC2024 Manual	Not Applicable	Non-squamous non-small cell lung cancer	469	IO+pemetrexed	wfuhlqmhvq(zeexkikedr) = itjhthyitk snoazbpazv (lmjzqhlnnd ) View more	Negative	09 Sep 2024
NCT00998166 (CTgov)	Phase 2	Advanced Lung Non-Squamous Non-Small Cell Carcinoma	12	Bevacizumab+Pemetrexed+Cisplatin	zkvbsnpmhy(dahmycmgnc) = jdwciwqmxb hdtrcmaaus (tyldfoyupk, gyudwtydmf - qkxweuibye) View more	-	30 Jul 2024

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