Investigational New Drugs最新文献

{"title":"Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort.","authors":"Oluwadunni E Emiloju, Jun Yin, Emily Koubek, Joel M Reid, Mitesh J Borad, Yanyan Lou, Mahesh Seetharam, Martin J Edelman, Edward A Sausville, Yixing Jiang, Ahmed O Kaseb, James A Posey, Sarah L Davis, Gregory J Gores, Lewis R Roberts, Naoko Takebe, Gary K Schwartz, Andrea E Wahner Hendrickson, Scott H Kaufmann, Alex A Adjei, Joleen M Hubbard, Brian A Costello","doi":"10.1007/s10637-024-01420-8","DOIUrl":"10.1007/s10637-024-01420-8","url":null,"abstract":"<p><p>Navitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib. In this phase 1 study, we evaluated the combination of navitoclax and sorafenib in a dose escalation cohort of patients with refractory solid tumors, with an expansion cohort in hepatocellular carcinoma (HCC). Maximum tolerated dose (MTD) was determined using the continual reassessment method. Navitoclax and sorafenib were administered continuously on days 1 through 21 of 21-day cycles. Ten patients were enrolled in the dose escalation cohort and 15 HCC patients were enrolled in the expansion cohort. Two dose levels were tested, and the MTD was navitoclax 150 mg daily plus sorafenib 400 mg twice daily. Among all patients, the most common grade 3 toxicity was thrombocytopenia (5 patients, 20%): there were no grade 4 or 5 toxicities. Patients received a median of 2 cycles (range 1-36 cycles) and all patients were off study treatment at data cut off. Six patients in the expansion cohort had stable disease, and there were no partial or complete responses. Drug-drug interaction between navitoclax and sorafenib was not observed. The combination of navitoclax and sorafenib did not increase induction of apoptosis compared with navitoclax alone. Navitoclax plus sorafenib is tolerable but showed limited efficacy in the HCC expansion cohort. These findings do not support further development of this combination for the treatment of advanced HCC. This phase I trial was conducted under ClinicalTrials.gov registry number NCT01364051.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"127-135"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells.","authors":"Mahtab Afsharzadeh, Jaleh Varshosaz, Mina Mirian, Farshid Hasanzadeh","doi":"10.1007/s10637-023-01409-9","DOIUrl":"10.1007/s10637-023-01409-9","url":null,"abstract":"<p><p>This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity. Targeted liposomes increased cytotoxicity on MCF-7 cells more significantly than NIH-3T3 cells. Cell flow cytometry indicated that targeted liposomes uptake was superior to plain (non-targted) liposomes and free drug. Free drug and RB-loaded liposomes interrupted cell cycle in G1. However, amino acid-targeted liposomes arrested cells more than the free drug at this stage. Targeted liposomes reduced cell cycle with more interruption in the G2/M phase compared to the negative control.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"89-105"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bispecific antibody targeting HER2 and CLDN18.2 eliminates gastric cancer cells expressing dual antigens by enhancing the immune effector function.","authors":"Jingying Yue, Shuai Shao, Jie Zhou, Wenting Luo, Yanling Xu, Qinbin Zhang, Jing Jiang, Marie M Zhu","doi":"10.1007/s10637-024-01417-3","DOIUrl":"10.1007/s10637-024-01417-3","url":null,"abstract":"<p><p>Gastric cancer (GC) is widely regarded as one of the toughest cancers to treat. Trastuzumab, which targets the human epidermal growth factor receptor 2 (HER2) for GC treatment, has demonstrated clinical success. However, these patients have a high likelihood of developing resistance. Additionally, Claudin18.2 (CLDN18.2) is a promising emerging target for GC treatment. Therefore, therapies that simultaneously target both HER2 and CLDN18.2 targets are of great significance. Here, we constructed a bispecific antibody targeting both HER2 and CLDN18.2 (HC-2G4S; BsAb), which displayed satisfactory purity, thermostability and enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) activity. In a tumor spheroids model of GC, BsAb demonstrated greater therapeutic efficacy than monoclonal antibodies (mAb) or combination treatment strategies. We propose that the enhanced anti-tumor potency of BsAbs in vivo is due to the monovalent binding of single-chain antibodies to more targets due to weaker affinity, resulting in a more potent immune effect function. Therefore, HC-2G4S could be a productive agent for treating GC that is HER2-positive, CLDN18.2-positive, or both, with the potential to overcome trastuzumab resistance and provide significant clinical benefits and expanded indications.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"106-115"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I/II trial of BMS-986,205 and nivolumab as first line therapy in hepatocellular carcinoma.","authors":"Jasmine C Huynh, May Cho, Arta Monjazeb, Ebaa Al-Obeidi, Amisha Singh, Kit Tam, Frances Lara, Anthony Martinez, Leslie Garcia, Edward J Kim","doi":"10.1007/s10637-023-01416-w","DOIUrl":"10.1007/s10637-023-01416-w","url":null,"abstract":"<p><strong>Background: </strong>Indoleamine-2,3-dioxygenase (IDO) helps orchestrate immune suppression and checkpoint inhibitor resistance in hepatocellular carcinoma (HCC). BMS-986,205 is a novel oral drug that potently and selectively inhibits IDO. This Phase I/II study evaluated the safety and tolerability of BMS-986,205 in combination with nivolumab as first-line therapy in advanced HCC.</p><p><strong>Methods: </strong>Adults with untreated, unresectable/metastatic HCC received BMS-986,205 at two dose levels (50-100 mg orally daily) in combination with fixed dose nivolumab (240mg/m² IV on Day 1 of each 14-day cycle). The primary objective was to determine the safety and tolerability of this combination; secondary objectives were to obtain preliminary efficacy.</p><p><strong>Results: </strong>Eight patients received a total of 91 treatment cycles in the dose escalation phase. All patients were Child Pugh A and 6 patients had underlying viral hepatitis. In the 6 evaluable patients, no dose-limiting toxicities (DLTs) were observed. The most common treatment-related adverse events (TRAEs) were aspartate transaminase (AST) and alanine transaminase (ALT) elevation (3 patients) and diarrhea, maculopapular rash and increased alkaline phosphatase (2 patients each). Grade 3 events were diarrhea and AST elevation (1 patient), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 patient). No grade 4-5 events occurred. Partial response was observed in 1 patient (12.5%) and stable disease in 3 patients (37.5%), yielding a disease control rate of 50%. Median PFS was 8.5 weeks; median OS was not reached.</p><p><strong>Conclusion: </strong>Combination BMS-986,205 and nivolumab showed a manageable safety profile with durable benefit as first-line therapy in a meaningful subset of advanced HCC patients.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"35-43"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.","authors":"Daiki Tsuji, Shigeru Nakagaki, Itsuki Yonezawa, Kenichi Suzuki, Takashi Yokokawa, Yohei Kawasaki, Takumi Yamaguchi, Takashi Kawaguchi, Masahiro Hatori, Takuma Matsumoto, Yukio Sakata, Keisuke Yamamoto, Tomoyasu Nishimura, Yuki Kogure, Toshinobu Hayashi, Misa Osawa, Kunihiko Itoh, Masaya Watanabe","doi":"10.1007/s10637-023-01414-y","DOIUrl":"10.1007/s10637-023-01414-y","url":null,"abstract":"<p><p>Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"44-52"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.","authors":"Meng-Ting Li, Yang He, Si-Yong Huang, Xiao Hu, Ji-Sheng Chen","doi":"10.1007/s10637-024-01421-7","DOIUrl":"10.1007/s10637-024-01421-7","url":null,"abstract":"<p><p>Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"116-126"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects","authors":"Hyun Chul Kim, Eunsol Yang, Soyoung Lee, Jaeseong Oh, Myongjae Lee, ChaeEun Lee, Kyoung Soo Ha, Won Sik Lee, In-Jin Jang, Kyung-Sang Yu","doi":"10.1007/s10637-023-01405-z","DOIUrl":"https://doi.org/10.1007/s10637-023-01405-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aim</h3><p>Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (C_max) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUC_last) of venadaparib for the fed to fasted state were 0.82 (0.7457–0.9094) and 1.02 (0.9088–1.1339) in Koreans, and 0.77 (0.6871–0.8609) and 0.96 (0.9017–1.0186) in Caucasians, respectively. No statistically significant differences were observed in C_max (<i>P</i>-value = 0.45) or AUC_last (<i>P</i>-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased C_max in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":"1 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138690750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage","authors":"Yue Wang, Xingyu Lin, Yue Wang, Guan Wang","doi":"10.1007/s10637-023-01415-x","DOIUrl":"https://doi.org/10.1007/s10637-023-01415-x","url":null,"abstract":"<p>In recent years, a number of novel pharmaceutical agents have received approval for the management of acute myeloid leukemia (AML). However, there is still ample opportunity for enhancing efficacy. The Wee1 inhibitor adavosertib (ADA) shows promise for the treatment of AML. Based on the effect of drugs on DNA damage, we conducted a combination study involving ADA and fimepinostat (CUDC-907), a dual inhibitor of PI3K and histone deacetylase (HDAC). We observed that the combination of CUDC-907 and ADA exhibited a synergistic effect in enhancing the antileukemic activity in both AML cell lines and primary patient samples, demonstrating through flow cytometry analysis and MTT assay, respectively. Additionally, our study revealed that CUDC-907 has the ability to augment ADA-induced DNA damage, as determined by the measurement of γH2AX levels and the implementation of the alkaline comet assay. Through the utilization of western blotting analyses, targeted inhibitors, and ectopic overexpression, we propose that the downregulation of Wee1, CHK1, RNR, and c-Myc are the potential mechanisms. Our data support the development of ADA in combination with CUDC-907 for the treatment of AML.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":"282 1 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138576471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RPTOR mutation: a novel predictor of efficacious immunotherapy in melanoma","authors":"Yanfang Jiang, Xintong Hu, Zhouyu Wang, Qin Zhang, Dongsheng Chen, Pingwei Zhao","doi":"10.1007/s10637-023-01413-z","DOIUrl":"https://doi.org/10.1007/s10637-023-01413-z","url":null,"abstract":"<p>Identifying biomarkers to evaluate the therapeutic effect of immune checkpoint inhibitors (ICIs) is crucial. Regulatory Associated Protein of MTOR Complex 1 (RPTOR), one of the genes in the mTOR pathway, plays a role in regulating tumor progression. However, the connection between RPTOR mutation and the efficacy of ICIs in melanoma remains unclear. The data of ICIs-treated melanoma patients in discovery (n = 384) and validation (n = 320) cohorts were obtained from cBioPortal databases. The genomic data in the two cohorts was used to investigate the connection between RPTOR mutation and immunotherapy efficacy. The underlying mechanisms were explored based on data from the The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort. Compared to melanoma patients with RPTOR wildtype (RPTOR-WT), RPTOR-mutation (RPTOR-Mut) patients achieved prolonged overall survival (OS) in both discovery cohort (median OS of 49.3 months vs. 21.7 months; HR = 0.41, 95% CI: 0.18–0.92; P = 0.026) and validation cohorts (not reached vs. 42.0 months; HR = 0.34, 95% CI: 0.11–1.06; P = 0.049). RPTOR-Mut melanoma patients exhibited a higher objective response rate (ORR) than RPTOR-WT patients in the discovery cohort (55.0% vs. 29.0%, P = 0.022). RPTOR-Mut patients exhibited higher TMB than RPTOR-WT patients in both discovery and validation cohorts (P &lt; 0.001). RPTOR-Mut melanoma patients had an increased number of DNA damage response (DDR) mutations in TCGA-SKCM cohort. Immune cell infiltration analysis suggested that activated CD4 memory T cells were more enriched in RPTOR-Mut tumors. RPTOR-Mut melanoma patients had higher expression levels of immune-related genes than the RPTOR-WT patients. Our results suggest that RPTOR mutation could serve as a predictor of effective immunotherapy for melanoma.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":"5 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics, diagnosis, treatment, and prognosis of nivolumab induced gastritis","authors":"Haibo Lei, Wei Sun, Xiang Liu, Chunjiang Wang","doi":"10.1007/s10637-023-01412-0","DOIUrl":"https://doi.org/10.1007/s10637-023-01412-0","url":null,"abstract":"<p>Gastritis has recently been reported to be associated with nivolumab, and the clinical characteristics of nivolumab induced gastritis remain unclear. To explore the clinical characteristics of nivolumab induced gastritis, and to provide reference for the classification and treatment guidelines of immune checkpoint inhibitors -related gastritis. Case reports, case series, and clinical studies of nivolumab induced gastritis were retrospectively analyzed by searching the database from the establishment of the database until September 30, 2023. Forty-seven were included, with a median age of 57 years (range 16, 93). The median time of symptom onset was 6 months (range 0.5,36) and 6.5 cycles (range 2, 62). Nausea (29 cases, 61.7%), vomiting (29 cases, 61.7%), and epigastric pain (28 cases, 59.6%) were the most common complaints. Esophagogastroduodenoscopy mainly showed erythema (28 cases, 59.6%). Gastric mucosa biopsy showed epithelial inflammatory cell infiltration (22 cases, 46.8%) and apoptosis (15 cases, 31.9%). Most patients’ symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether nivolumab was discontinued. Two patients died from gastritis related events. Gastritis should be considered as the cause of unexplained epigastric symptoms in the administration of nivolumab. Understanding the clinical features of nivolumab induced gastritis is very important for accurate diagnosis and timely management of these patients.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":"18 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}