Phase II Clinical Study of Irinotecan Liposome Combined with 5-FU/LV for the Patients with Advanced Pancreatic Cancer Who Failed to Receive Irinotecan-containing Regimens

This study is a prospective, single-arm, two-cohort phase II clinical study. It is expected to enroll 48 patients with advanced or metastatic pancreatic cancer who have failed prior treatment with irinotecan-containing regimens, including two cohorts: cohort 1 for patients who have progressed within 6 months of the end of adjuvant therapy for early pancreatic cancer with a prior irinotecan regimen or for patients with imaging-confirmed progression within 3 months of the end of first-line therapy for advanced patients, and cohort 2 for patients who have progressed after more than Cohort 2 was for patients who had progressed more than 6 months after adjuvant treatment with previous irinotecan regimen for early-stage pancreatic cancer or more than 3 months after the end of first-line treatment for advanced-stage patients. The study was conducted at the Cancer Prevention and Control Center of Sun Yat-sen University. The study consists of a screening period (within 28 days), a treatment period (until disease progression or intolerable toxicity occurs in patients), and a follow-up period (12 months, safety follow-up and PFS follow-up). Subjects signed informed consent and underwent baseline examinations during the screening period, and patients who met the inclusion exclusion criteria entered the treatment period, and all subjects perfected the relevant examinations specified in the protocol during the treatment to observe safety, tolerability and efficacy. The same subject received only one dosing schedule during the study period. After the treatment period was completed, a follow-up period was entered.

Start Date20 Nov 2024

Sponsor / Collaborator

Sun Yat-Sen University

ChiCTR2400088174 / SuspendedPhase 4IIT

Clinical research protocol on the efficacy and safety of microecological preparations in patients with chronic hepatitis B with low viral load after nucleoside drug treatment

Start Date01 Sep 2024

Sponsor / Collaborator

Affiliated Hospital of Xuzhou Medical University

CTR20232390 / RecruitingPhase 1/2

注射用SHR-A1811联合抗肿瘤药物在晚期实体瘤受试者中的安全性、耐受性及有效性的IB /II期临床研究

[Translation] Phase IB/II clinical study on the safety, tolerability and efficacy of SHR-A1811 for injection combined with anti-tumor drugs in subjects with advanced solid tumors

1.评估SHR-A1811联合吡咯替尼在Her-2表达的晚期实体瘤患者中的安全性、耐受性、初步疗效，确定II期推荐剂量。 2.评估SHR-A1811联合抗肿瘤药物治疗Her-2表达的晚期实体瘤的安全性、耐受性、初步疗效，确定II期推荐剂量。 3.评估SHR-A1811联合标准治疗，治疗Her-2表达的晚期实体瘤的安全性、耐受性、初步疗效，确定推荐剂量。

[Translation]

1. Evaluate the safety, tolerability, and preliminary efficacy of SHR-A1811 combined with pyrotinib in patients with advanced solid tumors expressing Her-2, and determine the recommended dose for Phase II. 2. Evaluate the safety, tolerability, and preliminary efficacy of SHR-A1811 combined with anti-tumor drugs in the treatment of advanced solid tumors expressing Her-2, and determine the recommended dose for Phase II. 3. Evaluate the safety, tolerability, and preliminary efficacy of SHR-A1811 combined with standard treatment for the treatment of advanced solid tumors expressing Her-2, and determine the recommended dose.

Start Date11 Aug 2023

Sponsor / Collaborator

Suzhou Suncadia Biopharmaceuticals Co., Ltd.

100 Clinical Results associated with Levofolinate Calcium

100 Translational Medicine associated with Levofolinate Calcium

100 Patents (Medical) associated with Levofolinate Calcium

314

Literatures (Medical) associated with Levofolinate Calcium

25 Jul 2024·Journal of the Anus Rectum and Colon

Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal Cancer (FANTASTIC Study)

Article

Author: Takamizawa, Yasuyuki ; Yasui, Masayoshi ; Ikeda, Masataka ; Kanemitsu, Yukihide ; Takase, Naoto ; Ensor, Joe ; Goto, Masahiro ; Jurdi, Adham ; Iwai, Takuma ; Kataoka, Kozo ; Shiozawa, Manabu ; Yamada, Takeshi ; Mori, Keita ; Yamazaki, Kentaro ; Takii, Yasumasa ; Matsuhashi, Nobuhisa ; Liu, Minetta C ; Sharma, Shruti ; Suto, Takeshi

Background:

The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown.

Methods/Design:

Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m², oxaliplatin 85 mg/m², l-leucovorin (l-LV) 200 mg/m², and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m² every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024.

Discussion:

This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches.

01 Feb 2024·AIDS research and human retroviruses

Factors Associated with Low-Level Viremia in People Living with HIV in the Italian Antiviral Response Cohort Analysis Cohort: A Case–Control Study

Article

Author: Paolucci, Stefania ; Bouba, Yagai Romeo ; Santoro, Maria Mercedes ; Callegaro, Anna Paola ; Rossetti, Barbara ; Bruzzesi, Elena ; Micheli, Valeria ; Maggiolo, Franco ; Ranzenigo, Martina ; Castagna, Antonella ; Lombardi, Francesca ; Costabile, Valentino ; Di Carlo, Domenico ; Bezencheck, Antonia ; Renica, Silvia ; Zoncada, Alessia

Despite effective antiretroviral therapies (ARTs), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e., 50-1,000 copies/mL). The present study compared PLWH experiencing LLV with those maintaining virological suppression (VS) and explored the potential impact of preexisting drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case-control study within a cohort of drug-experienced VS subjects from the Italian Antiviral Response Cohort Analysis database, followed in the period 2009-2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Preexisting drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they had experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4⁺ T cell count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL [adjusted odds ratio (aOR) (95% confidence interval [CI]) 1.30 (1.14-1.48)], a cumulative usage of both PI [aOR (95% CI): 2.03 (1.19-3.48)] and InSTI [aOR (95% CI): 2.23 (1.47-3.38)] and a cumulative GSS <2 [aOR (95% CI) 0.67 (0.46-0.98)], were associated with a higher risk in developing LLV. In current high-efficacy ART era, in drug-experienced PLWH, the predictors of increased risk of LLV were the presence of preexisting drug resistance, higher zenith VL, and previous PI, and InSTI exposure.

01 Feb 2024·HIV medicine

Effectiveness of intensive adherence counselling in achieving an undetectable viral load among people on antiretroviral therapy with low‐level viraemia in Uganda

Article

Author: Kiwanuka, Noah ; Makumbi, Fredrick ; Nalugoda, Fred ; Nasuuna, Esther ; Nakanjako, Damalie ; Nanyeenya, Nicholus ; Huzaifah, Mutyaba ; Kiyaga, Charles ; Kigozi, Godfrey ; Nakigozi, Gertrude ; Nabadda, Susan ; Kibira, Simon P. S.

Abstract:

Introduction:

Uganda was using a threshold of 1000 copies/mL to determine viral non‐suppression for antiretroviral therapy monitoring among people living with HIV, prior to this study. It was not clear whether people living with HIV with low‐level viraemia (LLV, ≥50 to <1000 copies/mL) would benefit from intensive adherence counselling (IAC). The purpose of this study was to determine the effectiveness of IAC among people living with HIV, receiving antiretroviral therapy, and with LLV in Uganda, to guide key policy decisions in HIV care, including the review of the viral load (VL) testing algorithm.

Methods:

This cluster‐randomized clinical trial comprised adults from eight HIV clinics who were living with HIV, receiving ART, and had recent VL results indicating LLV (tested from July 2022 to October 2022). Participants in the intervention arm clinics received three once‐monthly sessions of IAC, and those in the comparison non‐intervention arm clinics received the standard of care. At the end of the study, all participants were re‐tested for VL to determine the proportions of those who then had an undetectable VL (<50 copies/mL). We assessed the statistical association between cross‐tabulated variables using Fisher's exact test and then modified Poisson regression.

Results:

A total of 136 participants were enrolled into the study at eight HIV clinics. All 68 participants in the intervention arm completed all IAC sessions. Only one participant in the non‐intervention arm was lost to follow‐up. The average follow‐up time was 3.7 months (standard deviation [SD] 0.2) and 3.5 months (SD 0.1) in the intervention and non‐intervention arms, respectively.In total, 59 (43.7%) of 135 people living with HIV achieved an undetectable VL during the study follow‐up period. The effect of IAC on attaining an undetectable VL among people with LLV was nearly twice as high in the intervention arm (57.4%) than in the non‐intervention arm (29.9%): adjusted risk ratio 1.9 (95% confidence interval 1.0–3.5),p = 0.037.

Conclusion:

IAC doubled the likelihood of an undetectable VL among people living with HIV with LLV. Therefore, IAC has been instituted as an intervention to manage people living with HIV with LLV in Uganda, and this should also be adopted in other Sub‐Saharan African countries with similar settings.

ClinicalTrials.Gov Identifier:

NCT05514418.

News (Medical) associated with Levofolinate Calcium

28 Nov 2023

·www.prnewswire.com

Navigating the Evolving Market Dynamics of Bone Sarcoma: A Comprehensive Analysis of Osteosarcoma, Ewing Sarcoma, and Chondrosarcoma | DelveInsight

Each individual's risk of being diagnosed with primary bone sarcoma and their chances of recovery following diagnosis are influenced by a range of unique factors. In 2023, it is anticipated that 4K individuals of all ages in the United States will be diagnosed with primary bone sarcoma, including 2K males and 1.8K females. In 2020, approximately 400 cases were reported among those aged 15 to 19. LAS VEGAS, Nov. 28, 2023 /PRNewswire/ -- Bone sarcoma is a rare and aggressive form of cancer that originates in the bone tissue. It poses significant challenges during its treatment due to several factors. Firstly, its rarity often leads to delayed diagnosis, as symptoms can mimic other common conditions. Additionally, bone sarcoma typically affects children and young adults, making the emotional toll of the disease particularly challenging. Treatment often involves a combination of surgery, chemotherapy, and radiation therapy, which can be physically demanding and cause severe side effects. Moreover, because bone sarcoma tends to occur in the extremities, treatment may require complex and lengthy surgical procedures, potentially affecting mobility and quality of life. Furthermore, the risk of recurrence remains a constant concern, necessitating long-term monitoring and follow-up care. Despite these challenges, ongoing research and advancements in medical technology offer hope for improved outcomes and a better quality of life for those battling bone sarcoma. DelveInsight has recently released a series of epidemiology-based market reports focusing on benign bone sarcoma including Osteosarcoma Market Report, Ewing Sarcoma Market Report, and Chondrosarcoma Market Report. These reports include a comprehensive understanding of current treatment practices, historical and forecasted patient pool, emerging drugs, market share of individual therapies, and historical and forecasted market size from 2019 to 2032 segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Additionally, the reports feature exhaustive analysis of prominent companies working with their emerging candidates in different stages of clinical development. Let's deep dive into the assessment of these bone sarcoma markets individually. Osteosarcoma Market Osteosarcoma is a rare bone tumor affecting having an annual incidence of 3.4 cases per million. It is the most prevalent form of bone cancer, primarily developed in the osteoblast cells of bones, with a predilection for long bones near the knee joint. However, it can also manifest in other locations, including the upper leg, lower leg, upper arm, and virtually any bone in the body, including those in the pelvis, shoulder, and skull. It has the potential to invade adjacent tissues, such as tendons and muscles, and can metastasize to distant organs or other bones via the bloodstream. As per DelveInsight analysts, the total incident population of osteosarcoma in the 7MM was ~2K in 2022. The estimates show the highest incident cases of osteosarcoma in the United States with ~1K cases in 2022, and it is expected to increase by 2032. Osteosarcoma is commonly treated through a combination of chemotherapy, surgery, and radiation therapy. Despite some recent developments, limited progress has been achieved since the late 1980s when chemotherapy was added to surgical treatment, leading to improved survival rates. Radiation therapy impacts both normal and cancerous cells, causing various effects. Chemotherapeutic drugs like cisplatin, doxorubicin, ifosfamide, and high-dose methotrexate with leucovorin calcium rescue (HDMTX) are widely used. Additionally, a few FDA-approved products, such as FUSILEV and KHAPZORY, are available for osteosarcoma treatment. As per DelveInsight analysis, the osteosarcoma market size is expected to increase at a significant CAGR by 2032. This growth would be fuelled by the increase in the patient pool and the expected entry of emerging therapies. Osteosarcoma Pipeline Therapies and Companies Lenvatinib: Eisai Naxitamab: Y-mAbs Therapeutics BAY80-6946: Bayer Vactosertib: MedPacto For a comprehensive view of the osteosarcoma market, check out the Osteosarcoma Market Assessment Ewing Sarcoma Market Ewing Sarcoma, a malignant tumor, typically initiates its growth within the bones, with a higher incidence among children and young adults, often manifesting during adolescence. Although it can originate in any bone, it predominantly affects the long bones, such as the thigh bone, shin bone, and upper arm bone. The pelvis bones are also frequently involved. In some cases, the tumor may originate in muscle and soft tissues. Common symptoms include bone stiffness, pain, swelling, or tenderness, along with tissue surrounding the affected bone. As per the assessment done by DelveInsight, the total incident cases of Ewing sarcoma in the 7MM comprised approximately 1.2K cases in 2022 and are projected to increase during the forecasted period. The management of Ewing sarcoma typically adopts a comprehensive approach, which may encompass surgery, chemotherapy, and radiation therapy. The National Comprehensive Cancer Network (NCCN) offers specific chemotherapy regimens for localized and metastatic Ewing sarcoma. For first-line treatment, NCCN suggests VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide), VAIA (vincristine, doxorubicin, ifosfamide, and dactinomycin), and VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) for both initial presentations and as primary therapy for metastatic disease. In the second-line setting, NCCN recommends options like Cyclophosphamide and topotecan, Irinotecan + temozolomide ± Vincristine, Ifosfamide, carboplatin, etoposide, and Lurbinectedin. As per the latest Ewing Sarcoma Market Report, the total Ewing sarcoma market size in the 7MM is approximately USD 26 million in 2022 and is projected to increase during the forecast period (2023–2032). The expected introduction of upcoming therapies and the deepened integration of early patient screening, medication management in secondary care, and diverse clinical setups, ongoing research into optimal implementation approaches, and a surge in public awareness will ultimately pave the way for the advancement of efficient treatment choices. Ewing Sarcoma Pipeline Therapies and Companies SECLIDEMSTAT (SP-2577): Salarius Pharmaceuticals ZEPZELCA (LURBINECTEDIN): Jazz Pharmaceuticals and PharmaMar VERZENIO (ABEMACICLIB): Eli Lilly IBRANCE (PALBOCICLIB): Pfizer MECBOTAMAB VEDOTIN (BA3011): Bioatla IOPOFOSINE I 131 (CLR 131): Cellectar Biosciences TP-1287: Sumitomo Pharma Oncology NBRX-109: Inhibrx Explore in-depth for a comprehensive understanding of the Ewing Sarcoma Clinical Trials Chondrosarcoma Market Chondrosarcoma comprises a group of bone tumors originating from cells that overproduce cartilage. Among these tumors, conventional chondrosarcoma is the most frequent type and is generally associated with slow growth. Conversely, rarer subtypes like dedifferentiated chondrosarcoma, myxoid chondrosarcoma, clear cell chondrosarcoma, and mesenchymal chondrosarcoma tend to exhibit a more aggressive growth pattern and have the potential to spread to distant body parts. DelveInsight estimated that the total incident cases of chondrosarcoma in the 7MM comprised approximately 2K cases in 2022 and are projected to increase during the forecasted period. The management approach for chondrosarcoma is contingent upon factors like tumor type, grade, and location, with the grading system serving as the most reliable indicator of clinical prognosis. It is firmly established that surgical intervention remains the gold standard and sole effective treatment for chondrosarcoma, as alternative modalities such as radiotherapy and chemotherapy exhibit limited responsiveness and resistance. Surgical options encompass curettage, radical resection, and amputation, each necessitating comprehensive clinical judgment and contingent upon variables such as lesion size, location, and malignant characteristics. Anticipated advancements in upcoming therapies and increased integration of early patient screening and medication within secondary care and other clinical settings, along with ongoing research to determine the best implementation methods, are expected to contribute to the development of more effective treatment options. However, chondrosarcoma, being an orphan disease, presents challenges in conducting clinical trials. Limited outcome data for locally advanced or metastatic patients underscore the need for new treatment approaches. Phase I trials, due to their small number of chondrosarcoma patients at varying dose levels, make it difficult to draw definitive conclusions. Nevertheless, some Phase II trials have yielded promising results, warranting further investigation. Encouraging retrospective studies could help augment the currently limited data. Urgent efforts to boost research studies on this orphan disease are imperative. As per DelveInsight analysis, the total market size of chondrosarcoma in the 7MM is approximately USD 9 million in 2022 and is projected to increase at a massive CAGR of 24.8% due to increasing awareness of the disease and the launch of the emerging therapy. Chondrosarcoma Pipeline Therapies and Companies INBRX-109: Inhibrx To access a complete analysis of the chondrosarcoma market, visit Chondrosarcoma Market Assessment Trending Oncology Reports Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies, including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. Non-Hodgkin Lymphoma Market Non-Hodgkin Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NHL companies, including GAbbVie, Genmab, Novartis, Angiocrine Bioscience, Autolus, Zentera Therapeutics, Jiangsu Hengrui Medicine, among others. Oncolytic Virus Cancer Therapies Market Oncolytic Virus Cancer Therapies Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key oncolytic virus cancer therapies companies, including Targovax, Replimune, Genelux Corporation, Candel Therapeutics, DNAtrix, SillaJen, Treovir, Lokon Pharma AB, Istari Oncology, CG Oncology, Amgen, Daiichi Sankyo, among others. Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda, among others. Oncology Conference Coverage Services DelveInsight's Oncology Conference Coverage Services deliver a comprehensive examination of conference outcomes from a range of prominent events, such as ASCO, ESMO, ASH, AACR, ASTRO, SOHO, SITC, European CAR T-cell Meeting, and IASLC 2023. This in-depth analysis equips businesses with the insights they need for effective competitive intelligence and forecasting market trends, aiding in the development of future strategies. About DelveInsight DelveInsight is a leading healthcare-focused market research and consulting firm that provides clients with high-quality market intelligence and analysis to support informed business decisions. With a team of experienced industry experts and a deep understanding of the life sciences and healthcare sectors, we offer customized research solutions and insights to clients across the globe. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Phase 2Clinical ResultRadiation TherapyASCO

23 Aug 2023

·www.sciencedaily.com

A new targeted treatment shows promise for select patients with stomach cancer

An international phase 3 clinical trial found that a new targeted treatment called zolbetuximab, given in combination with a standard chemotherapy, extended survival for patients with advanced gastric or gastroesophageal junction cancer that overexpressed a specific biomarker. An international phase 3 clinical trial, done in participation with Weill Cornell Medicine and NewYork-Presbyterian, found that a new targeted treatment called zolbetuximab, given in combination with a standard chemotherapy, extended survival for patients with advanced gastric or gastroesophageal junction cancer that overexpressed a specific biomarker. Results from the GLOW study, published July 31 in Nature Medicine, together with results from the parallel SPOTLIGHT study that evaluated zolbetuximab with an alternative standard chemotherapy, prompted the United States Food and Drug Administration to grant priority review to the manufacturer's biologic license application and set January 12, 2024, as the target decision date. If approved, zolbetuximab will be the first targeted therapy in the U.S. for patients with previously untreated advanced gastric or esophageal junction cancer that is human epidermal growth factor receptor 2 (HER2)-negative and overexpresses the protein claudin-18 isoform 2 (CLDN 18.2). Gastric cancer is the fifth most diagnosed cancer globally, and its incidence has increased markedly in the last few decades. Patients with cancer of the stomach or at the junction where the esophagus joins the stomach, known as the gastroesophageal junction, typically have few symptoms in early disease stages, so most are diagnosed after the cancer has advanced or become metastatic. According to the National Cancer Institute, the five-year survival rate for patients with metastatic disease is about 7 percent. There are few targeted treatments available for patients with gastric and gastroesophageal cancers: Patients with tumors expressing the programmed cell death ligand 1 protein can be treated with immunotherapy, and those with HER2-positive tumors can be treated with trastuzumab, also known by the trade name Herceptin. There is another group of HER2-negative patients who fit neither category, and for whom targeted therapies aren't generally used. However, these gastric cancers tend to have higher levels of CLDN 18.2, which is normally found in gastric mucosa cells and becomes more exposed as gastric cancer develops. Zolbetuximab is a monoclonal antibody, administered intravenously, that binds to CLDN18.2, killing the dividing cancer cells directly and also alerting the immune system to respond. "Currently, standard chemotherapy regimens are the only treatment options for many patients with HER2-negative and low PD-L1 gastric and gastroesophageal cancer, and survival is about 12 months," said lead study author and trial co-principal investigator Dr. Manish Shah, the Bartlett Family Professor of Gastrointestinal Oncology and director of the Gastrointestinal Oncology Program in the Division of Hematology and Medical Oncology at Weill Cornell Medicine. "A new treatment for these patients would address a significant unmet need to extend survival." The GLOW study was conducted between November 2018 and February 2022 at 166 sites, including NewYork-Presbyterian/Weill Cornell Medical Center, across 18 countries. A total of 507 patients with previously untreated HER2-negative locally advanced or metastatic gastric or gastroesophageal junction cancer expressing CLDN18.2 were randomized to receive zolbetuximab in combination with capecitabine plus oxaliplatin chemotherapy (CAPOX) or a placebo plus CAPOX. Zolbetuximab plus CAPOX significantly increased progression-free survival compared with placebo plus CAPOX. Specifically, zolbetuximab plus CAPOX lowered the risk of disease progression or death by 31 percent compared with placebo plus CAPOX. The median progression-free survival was 8.21 months for patients in the zolbetuximab group compared with 6.8 months for those in the placebo group. Furthermore, the addition of zolbetuximab doubled the chance of not having disease progression at 2 years (from 7 percent with placebo versus 14 percent with zolbetuximab). Results also demonstrated that zolbetuximab plus CAPOX significantly lengthened overall survival and reduced the risk of death by 23 percent. The median overall survival was 14.4 months for patients in the zolbetuximab plus CAPOX group versus 12.2 months for those in the placebo plus CAPOX group. Long terms survival similarly increased significantly with the addition of zolbetuximab -- 29 percent survival at 2 years with zolbetuximab versus 17 percent with placebo. Treatment-related adverse events were similar between groups, with nausea, vomiting and decreased appetite reported most frequently. "These side effects were as expected," said Dr. Shah, who is also chief of the Solid Tumor Oncology Service and co-director of the Center for Advanced Digestive Care at NewYork-Presbyterian/Weill Cornell Medical Center and a member of the Sandra and Edward Meyer Cancer Center and of the Englander Institute for Precision Medicineat Weill Cornell Medicine. "It was good to see zolbetuximab did not add significant toxicity." Similarly, a study published in The Lancet May 20, 2023 reported strong survival outcomes for the international phase 3 SPOTLIGHT trial that evaluated zolbetuximab in combination with a different chemotherapy regimen consisting of modified folinic acid or levofolinate, fluorouracil and oxaliplatin (mFOLFOX). Dr. Shah was a member of the SPOTLIGHT steering committee, co-author of The Lancet paper and involved in designing both the GLOW and SPOTLIGHT trials, which were sponsored by Astellas Pharma, the maker of zolbetuximab. "We now have evidence from two large trials showing that the addition of zolbetuximab provides a meaningful survival benefit for patients with CLDN 18.2-positive gastric cancers," he said. "If zolbetuximab is approved, patients will be able to decide with their physicians whether zolbetuximab plus CAPOX or mFOLFOX is the right regimen for them."

Clinical ResultPhase 3Priority ReviewASCO

100 Deals associated with Levofolinate Calcium

External Link

KEGG	Wiki	ATC	Drug Bank
D04715	Levofolinate Calcium	V03AF04	DBSALT001886

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Small intestine carcinoma	JP	Pfizer Japan, Inc.	21 Sep 2018
Pancreatic Cancer	JP	Pfizer Japan, Inc.	20 Dec 2013
Drug intoxication	US	Acrotech Biopharma LLCStartup	07 Mar 2008
Osteosarcoma	US	Acrotech Biopharma LLCStartup	07 Mar 2008
Colorectal Cancer	JP	Pfizer Japan, Inc.	14 Feb 2005
Stomach Cancer	JP	Pfizer Japan, Inc.	16 Jun 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Stage III Colon Cancer	Phase 3	JP	Wyeth AB	01 Oct 2002
recurrent gastric cancer	Phase 3	JP	Wyeth AB	01 May 2002
Recurrent Non-Small Cell Lung Cancer	Phase 1	-	Acrotech Biopharma LLCStartup	01 Apr 2013
Mucositis	Phase 1	-	Acrotech Biopharma LLCStartup	01 Mar 2013
Non-Hodgkin's lymphoma refractory	Phase 1	-	Acrotech Biopharma LLCStartup	01 Mar 2013

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02394795 (PARADIGM, CTgov)	Phase 3	NRAS Wild-type Colorectal Cancer	823	levofolinate calcium+oxaliplatin+panitumumab+5-FU (Group P; mFOLFOX6 + Panitumumab Combination Therapy)	yspyyxyekx(stahgxetal) = hclxstmhlo szncelvekw (ghltqwfsez, wqxbwvxuhc - zmqydnjsnk) View more	-	01 Nov 2023
NCT02394795 (PARADIGM, CTgov)	Phase 3	NRAS Wild-type Colorectal Cancer	823	levofolinate calcium+bevacizumab+oxaliplatin+5-FU (Group B; mFOLFOX6 + Bevacizumab Combination Therapy)	yspyyxyekx(stahgxetal) = mquupfvccw szncelvekw (ghltqwfsez, xytysaxqpv - qxpxhdaick) View more	-	01 Nov 2023
ASCO_GI2015	Phase 2	Adenocarcinoma	24	mFOLFOX6 regimen	uzeaggcpaq(bjebudrzbo) = rdqtqtdskn ohyhiitfxp (tzeirxnywm ) View more	-	20 Jan 2015

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