Why is HER2 expression important in patients with urothelial carcinoma? preliminary safety and efficacy results of RC48 combined with toripalimab in patients wit local advaned or metastatic Urothelial carcinoma(NCT04264936,RC48-C014), An Open-label, Single-arm, Multicenter, Phase II Study of RC48 to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer (NCT03809013,RC48-C009), Antitumor activity of neoadjuvant treatment with enfortumab vedotin monotherapy in patients with muscle invasive bladder cancer (MIBC) who are cisplatin-ineligible. Introduction Bladder cancer is the tenth most prevalent cancer worldwide and is much more common in males than in females [1 ]. WBC: White blood cell, Neu: Neutrophil count (A). Listing a study does not mean it has been evaluated by the U.S. Federal Government. There have been data published showing that HER2-expressing urothelial tumors are often associated with higher grade, higher stage, and potentially adverse clinical outcomes. Why Should I Register and Submit Results? Enfortumab vedotin is an antibody-drug conjugate (ADC) directed to Nectin-4, which is highly expressed in bladder tumors. To identify potential therapeutic targets, IHC staining for HER2 was performed. Surgical plan: radical cystectomy + urinary diversion. In a case [29], it was reported that DV in a 52-year-old HER2 (2+) patient with advanced lung adenocarcinoma after failure of first-line therapy improved both lung lesions and brain lesions. In 2022, the commercialization has . DV adopts a novel HER2 monoclonal antibody, Hertuzumab, which has a great affinity for HER2 targets and has the potential to treat cancers with low or even unstable HER2 expression [24]. Burger M., Catto J.W.F., Dalbagni G., Grossman H.B., Herr H., Karakiewicz P., et al. The age on the date of signing the informed consent form is 18 to 75 years old. Li J., Juliar B., Yiannoutsos C., Ansari R., Fox E., Fisch M.J., et al. However, some patients cannot tolerate platinum-based regimens. Disitamab vedotin (RC-48) is under development for the treatment of solid tumors including HER2 expressing non-small cell lung cancer, non-muscle invasive bladder cancer (NMIBC), metastatic liver cancer, advanced or metastatic urothelial carcinoma of unresectable origin including urothelial carcinoma of bladder, . Disitamab vedotin demonstrated promising efficacy with a tolerable safety profile in patients with HER2-negative metastatic urothelial carcinoma. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Grossman H.B., Natale R.B., Tangen C.M., Speights V.O., Vogelzang N.J., Trump D.L., et al. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., et al. Abnormal symptoms such as hair loss, fatigue, and hypoesthesia were also recorded. Part of the tumor on the right lateral bladder wall was resected and sent for pathological examination. ), etc. How much HER2 expression is enough to get uptake into the tumor cell? We report an MIBC case with severe renal insufficiency treated by neoadjuvant therapy with gemcitabine and Disitamab Vedotin. official website and that any information you provide is encrypted Overall survival (OS) is defined as the time from the start of treatment to death from any cause. I think of these as a new class of targeted agents that more directly target tumor cells. About Brief Summary This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. a. eGFR: estimated glomerular filtration rate, ALT: alanine aminotransferase, AST: aspartate aminotransferase, NT-proBNP: N-terminal pro-B-type natriuretic peptide, cTnI: cardiac troponin I. The FDA has granted disitamab vedotin (RC48) a breakthrough therapy designation for the treatment of patients with HER2-positive locally advanced or metastatic urothelial carcinoma following treatment with platinum-based chemotherapy, according to RemeGen, the company developing the antibody-drug conjugate (ADC). Neoadjuvant therapy with Disitamab vedotin in treating muscle-invasive bladder cancer: A case report. Dindo D, Demartines N, Clavien PA. Study participants received 2.0 mg/kg of intravenous disitamab vedotin once every 2 weeks until disease progression, intolerable toxicity, patient decision, or death. The median progression-free survival (PFS) and OS were 4.1 months and 7.9 months, respectively [28]. Inclusion in an NLM database does not imply endorsement of, or agreement with, Another clinical trial was conducted to evaluate the efficacy and safety of intravenous DV in patients with locally advanced or metastatic HER2-negative urothelial carcinoma ({"type":"clinical-trial","attrs":{"text":"NCT04073602","term_id":"NCT04073602"}}NCT04073602). Disitamab vedotin is a novel ADC that selectively delivers the anti-cancer agent monomethyl auristatin E (MMAE) into HER2-expressing tumor cells. Significant adverse side effects did not occur during neoadjuvant therapy. 1(A and B)]. Platinum-based regimens are regarded as the preferred alternative for neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC) patients. 4(A and B)]. National Cancer Institute. The imaging results before neoadjuvant therapy showed that the maximum diameter of the lesion was approximately 80 mm. The site is secure. Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing Chinese and global burdens of gastric cancer from 1990 to 2019. Keywords Neoadjuvant therapy Muscle-invasive bladder cancer Disitamab vedotin HER2-Targeted Antibodydrug conjugates 1. In 2022, the commercialization has . Immunotherapy, such as pembrolizumab or atezolizumab, is reported to treat PDL1-positive, unresectable, metastatic and platinum-ineligible bladder cancer patients [14,15]. For MIBC patients, neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) and pelvic lymph node dissection (PLND) is usually recommended. Given by IV on Day 1 of each 6-week cycle. S1. Bellmunt risk score was 0 for 9 (47.3%) patients, 1 for 4 (21.1%) patients, 2 for 4 (21.1%) patients, and 3 for 2 (10.5%) patients. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (obtained 14 days prior to enrollment): a. In addition, the patients did not suffer from obvious drug-related adverse symptoms. Cisplatin-ineligible patients were defined as those with at least one of the following [13]: performance status >1; GFR <60 ml/min; grade >2 audiometric hearing loss; grade >2 peripheral neuropathy or New York Heart Association class III heart failure. According to the assessment by the investigator, the need for radical cystectomy after neoadjuvant therapy, and the indications for radical cystectomy are met, and they are willing to undergo the surgery. This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. The time from start of study treatment or randomization (if applicable) to the date of death due to any cause. Advances in her2-targeted therapy: novel agents and opportunities beyond breast and gastric cancer. The role of neoadjuvant immunotherapy for platinum-ineligible patients remains to be investigated. Open-label, multicenter, phase ii study of rc48-adc, a her2-targeting antibodydrug conjugate, in patients with locally advanced or metastatic urothelial carcinoma. Serious infection requiring systemic antibacterial, antifungal or antiviral treatment within 14 days before enrollment (HBV infection is performed according to the instructions of exclusion criterion 12). Neoadjuvant therapy with Disitamab vedotin in treating muscle-invasive Novel her2targeted therapies for her2positive metastatic breast cancer. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Magnetic resonance imaging scanning of the bladder after neoadjuvant therapy. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicenter, phase 2 trial. Disitamab vedotin is under clinical development by Seagen and currently in Phase II for Bladder Cancer. On this episode of Managed Care Cast, we bring you an excerpt of an interview with a co-chair of the 2022 Cholangiocarcinoma Foundation (CCF) annual conference, held earlier this year, about the significant unmet therapy needs facing most patients with this rare cancer. Understanding the Unmet Need for Therapies to Treat Rare Bile Duct Cancer. Conclusions Keywords Neoadjuvant therapy Muscle-invasive bladder cancer Disitamab vedotin HER2-Targeted Antibodydrug conjugates 1. A new HER2-directed antibody drug conjugate, disitamab vedotin, showed promising results with high-response rates in HER2 high and low bladder cancer. Cohorts A, B, C, and D will enroll simultaneously. Humphrey P.A., Moch H., Cubilla A.L., Ulbright T.M., Reuter V.E. Note: Inactive hepatitis B surface antigen carriers or patients with stable active HBV infection (HBV DNA <500 IU/mL [2500 copies/mL]) after continuous antiviral therapy can be enrolled. Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase ii hoosier oncology group study. This antibody-drug conjugatemuch like enfortumab vedotin [Padcev], which targets nectin-4 expressionbrings monomethyl auristatin E more directly to HER2-overexpressing tumors. Known allergy to any study drug or excipient. One prior line of platinum-containing chemotherapy. Xu Y, Wang Y, Gong J, Zhang X, Peng Z, Sheng X, Mao C, Fan Q, Bai Y, Ba Y, Jiang D, Yang F, Qi C, Li J, Wang X, Zhou J, Lu M, Cao Y, Yuan J, Liu D, Wang Z, Fang J, Shen L. Gastric Cancer. Treatment of patients with metastatic urothelial cancer "unfit" for cisplatin-based chemotherapy. The proportion of participants who have achieved objective response (confirmed CR or PR as per RECIST v 1.1 criteria) or SD lasting at least 5 weeks. Bookshelf Accessed June 30, 2022. Patients who tested negative for HCV antibodies during the screening period, or those who tested negative for HCV RNA after positive HCV antibody tests could be enrolled. Its a trial looking at disitamab vedotin, which is another antibody-drug conjugate using that very toxic tubulin agent, monomethyl auristatin E. But in this case, the antibody targets HER2 expression. Representative hematoxylin-eosin staining of tumor tissues from radical cystectomy (A), magnification:200. Then, endocytosis occurs and leads to agent internalization. It can be delivered to tumor tissues after targeting antibodies. Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy. The median duration of response was 4.3 months (95% CI, 2.7not evaluable). Then, RC with PLND was performed on April 12, 2022, and the postoperative pathological findings proved high-grade invasive urothelial carcinoma involving the bladder lamina propria with HER2 (IHC 1+) [Fig. Yin M., Joshi M., Meijer R.P., Glantz M., Holder S., Harvey H.A., et al. Please enable it to take advantage of the complete set of features! Neoadjuvant regimen (up to 4 cycles): Disitamab Vedotin for Injection, 2.0 mg/kg, given as an IV infusion on day 1, and Penpulimab Injection, 200 mg, on every 21 days On day 1 of the cycle, it is given as an intravenous infusion. Written informed consent for publication was obtained from this patient. A Look at Racial Disparities in US HPV Vaccine Uptake. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment. I look forward to seeing the outcomes of this clinical trial as it accrues patients using this novel method of bringing a very toxic tubulin agent directly to that HER2-expressing tumor. HER2-targeted agents have also been reported to treat bladder cancer [7]. ClinicalTrials.gov Identifier: NCT04879329, Interventional Neoadjuvant therapy with Disitamab vedotin in treating - ScienceDirect Visit. Cancer stat facts: bladder cancer. Comparison of two ICI-based microtubule antagonist therapies for high RemeGen Demonstrates Profitability to Successfully Receive Approval government site. As of the data cutoff of May 5, 2022, the confirmed objective response rate (ORR) with the agent was 26.3% (95% CI, 9.1%-51.2%), with all 5 responders experiencing partial responses. National Library of Medicine ESMO 2022: Advanced or Metastatic Urothelial Cancer. Epub 2021 Apr 22. https://doi.org/10.1016/j.heliyon.2023.e15157. Antibody-drug conjugates (ADC), a combination of cytotoxic drugs and antibodies, have emerged as a rising star in cancer therapy. Patients who do not tolerate cisplatin chemotherapy must meet at least one of the following criteria: The patient's organ function is good, as measured by the following screening laboratory values ?? After neoadjuvant therapy with DV and gemcitabine, the lesion significantly shrunk. It consists of three regions, including an N-terminal extracellular domain (ECD), a single -helical transmembrane domain, and an intracellular tyrosine kinase domain. This patient was pathologically confirmed to have invasive high-grade papillary urothelial carcinoma of the bladder with HER2 (IHC 1+) [Fig. Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, Shi B, Liu J, He Z, Yu G, Ying J, Han W, Hu C, Ling Y, Chi Z, Cui C, Si L, Fang J, Zhou A, Guo J. Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. This study is a multicenter, open-label, single-arm prospective clinical study to evaluate the neoadjuvant treatment of Disitamab Vedotin for Injection combined with Penpulimab Injection in cisplatin-intolerant cT2-T4aNxM0 bladder urothelial carcinoma Efficacy and safety in patients. It brings to mind the question: how much targeting is enough? Miyazaki J., Nishiyama H. Epidemiology of urothelial carcinoma. The .gov means its official. In this review, we will analyze the structural elements and mechanisms of RC48. Disitamab Vedotin in Subjects With HER2 Expressing Urothelial Carcinoma Disitamab vedotin is a promising antibody-drug conjugate option undergoing evaluation for patients with metastatic urothelial cancer. Representative immunohistochemical staining for HER2 in tumor tissues from transurethral resection of bladder tumor (B), magnification:200. Disitamab Vedotin (DV) is a novel humanized anti-HER2 antibody-drug conjugate (ADC), has been approved for metastatic urothelial carcinoma and gastric cancer in China. In the second abstract, titled The efficacy and safety of antibody drug conjugate for high-risk non-muscle-invasive bladder cancer, disitamab vedotin was administered as a monotherapy or combined with tislelizumab. Disitamab Vedotin granted FDA breakthrough therapy designation in This paper aims to offer a general insight and summary of the mechanism of action and the currently completed and ongoing clinical studies of RC-48 in HER-2 positive solid tumors. An anti-her2 antibody conjugated with monomethyl auristatin e is highly effective in her2-positive human gastric cancer. Therefore, gemcitabine combined with DV in neoadjuvant therapy was effective and safe for this patient. Update JAVELIN 100 Bladder study ASCO 2023: RemeGen Exhibits Promising Results of Disitamab Vedotin in Additionally, the median progression-free survival with disitamab vedotin was 5.5 months (95% CI, 3.9-6.8), and the median overall survival was 16.4 months (95% CI, 7.1-21.7). and transmitted securely. Received other approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin 2 and tumor necrosis factor) within 28 days before enrollment. Long-term use of large amounts of hormones or other immunosuppressive agents is required, and the investigator evaluates that it has an impact on the study treatment. Patients with an IHC score of 0 (n = 6) had no response to therapy. Cohort E will begin enrollment after Cohort D participants have completed the DLT evaluation period. 2021 Jan 1;27(1):43-51. doi: 10.1158/1078-0432.CCR-20-2488. However, platinum agents have certain nephrotoxicity. The results of the blood test during therapy are provided in Fig. However, in NAC, it is not mentioned. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Schwartz L.H., Litiere S., de Vries E., Ford R., Gwyther S., Mandrekar S., et al. YANTAI, China , June 5, 2023 /PRNewswire/ -- RemeGen Co., Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, announced the latest clinical research results on disitamab vedotin (RC48) at this year's American Society of Clinical Oncology (ASCO) Annual Meeting, taking place June 2-6, 2023 , in Chica. For decades, weve had systemic chemotherapy, but it took the development of a class of novel agentsimmune checkpoint inhibitorsbefore we had additional agents approved for bladder cancer. Stockwatch Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, and C) [TimeFrame:Duration of treatment; approximately 2 years], Incidence of adverse events (AEs) (Cohorts D and E) [TimeFrame:Approximately 2 years], Incidence of dose alterations (Cohorts D and E) [TimeFrame:Approximately 2 years], Incidence of laboratory abnormalities (Cohorts D and E) [TimeFrame:Approximately 2 years], Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E) [TimeFrame:Approximately 2 years], Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E) [TimeFrame:Approximately 2 years], Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Maximum concentration (Cmax) (Cohorts D and E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Trough concentration (Ctrough) (Cohorts D and E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) [TimeFrame:Duration of treatment; approximately 2 years], Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], PFS per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], DCR per RECIST v1.1 by investigator (Cohorts A, B, and C) [TimeFrame:From start of treatment to completion of response assessment; approximately 2 years], Overall survival (OS) (Cohorts A, B, and C) [TimeFrame:Duration of study; approximately 3 years], Incidence of adverse events (AEs) (Cohorts A, B, and C) [TimeFrame:Approximately 2 years], Incidence of dose alterations (Cohorts A, B, and C) [TimeFrame:Approximately 2 years], Incidence of laboratory abnormalities (Cohorts A, B, and C) [TimeFrame:Approximately 2 years], Incidence of ECG abnormalities (Cohorts A, B, and C) [TimeFrame:Approximately 2 years], Change from baseline of LVEF (Cohorts A, B, and C) [TimeFrame:Approximately 2 years], PK parameter - AUC (Cohorts A, B, and C) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Cmax (Cohorts A, B, and C) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Tmax (Cohorts A, B, and C) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter - Ctrough (Cohorts A, B, and C) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], PK parameter of pembrolizumab - Cmax (Cohort E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], Incidence of anti-drug antibodies (ADAs) against disitamab vedotin (All Cohorts) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], Incidence of anti-drug antibodies (ADAs) against pembrolizumab (Cohorts C and E) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], Incidence of neutralizing antibodies (NABs) against disitamab vedotin (All Cohorts) [TimeFrame:Through 30-37 days following the last dose of DV; up to approximately 2 years], Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra, Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy. within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B), Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia), Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy, Major surgery that has not fully recovered within 4 weeks prior to dose administration, Peripheral sensory or motor neuropathy Grade 2 at baseline, Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components, Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) RemeGen Demonstrates Profitability to Successfully Receive Approval within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D), Any prior history of Grade 3 non-hematological AEs related to prior therapy, Peripheral sensory or motor neuropathy Grade 1 at baseline, Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) If the subject does not withdraw from the trial voluntarily, the toxic and side effects caused by the drug are intolerable, or the investigator believes that the subject is not suitable for further trials, each subject will undergo the following treatment after surgery, and in Efficacy evaluation and follow-up were performed in each cycle. Additionally, the agent has demonstrated superior antitumor activity vs other treatments when examined in animal models. The .gov means its official. Unauthorized use of these marks is strictly prohibited. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04879329, We're building a modernized ClinicalTrials.gov! Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05488353, We're building a modernized ClinicalTrials.gov! These promising results for HER2-negative tumors inspired us to tentatively use DV in this case. (UroToday.com) In the Urothelial Cancer poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Koshkin presented the rationale and design of a novel trial in progress of Disitamab vedotin (DV; RC48-ADC) is an investigational antibody-drug conjugate (ADC) comprised of a HER2-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a . According to the imaging examinations, the lesions were significantly reduced after receiving neoadjuvant therapy. Conclusions In this T3N0M0 cisplatin-ineligible patient, gemcitabine combined with DV as neoadjuvant therapy achieved radiological partial response, and no significant adverse events were observed during neoadjuvant therapy. Flaig T.W., Spiess P.E., Abern M., Agarwal N., Bangs R., Boorjian S.A., et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the abacus trial. A phase II trial of DV, which enrolled patients with locally advanced or metastatic gastric or gastroesophageal junction cancer, showed promising outcomes. Bladder cancer is the most common cancer in the urinary system [10]. On admission, the estimated glomerular filtration rate was 21.4 ml/min/1.73 m2, and the creatinine level was 255 mol/L, which was considered to indicate chronic kidney disease 4 [8]. This patient received neoadjuvant therapy with gemcitabine combined with Disitamab Vedotin (DV), a novel antibodydrug conjugate (ADC) of HER2. At present, these drugs are mainly used for the treatment of breast cancer and gastroesophageal cancer with positive HER2 expression [20,21]. CA Cancer J Clin. Disitamab vedotin (RC48-ADC) demonstrated promising efficacy with a tolerable safety profile in patients with HER2-negative metastatic urothelial carcinoma, according to results from the phase 2 RC48-C011 trial (NCT04073602) presented during the 2022 ASCO Annual Meeting.1. Stadler W.M., Kuzel T., Roth B., Raghavan D., Dorr F.A. Known hypersensitivity to disitamab vedotin or any of their components, Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. Seagen and RemeGen Announce Exclusive Worldwide License and Co Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Notably, serum creatinine was decreased during therapy. Disitamab Vedotin Combined With PD-1 and Neoadjuvant Chemotherapy for Is there a potential bystander effect? Perhaps you get enough drug into the low-expressing tumor cells and the tumor cells are killed, releasing drug in the circulation nearby thats taken up in nearby cells or tumor cells that dont have HER2 expression. RemeGen Announces US FDA Has Granted Breakthrough Therapy - BioSpace History of potassium, sodium, calcium abnormalities or hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases, including diabetes, hypertension, cardiovascular disease, that the investigator believes may affect treatment (such as active heart disease within 6 months before enrollment, including: severe/unstable angina pectoris, myocardial infarction, symptomatic congestive heart failure and ventricular arrhythmia requiring drug treatment, etc. Phase i study of the recombinant humanized anti-her2 monoclonal antibody-mmae conjugate rc48-adc in patients with her2-positive advanced solid tumors. In NAC, cisplatin-based multiagent neoadjuvant chemotherapy shows 5% and 9% absolute improvement in 5-year overall survival (OS) and disease-free survival (DFS), respectively [3], and it is regarded as the preferred and recommended regimen by clinical guidelines [[4], [5], [6]]. Would you like email updates of new search results? An official website of the United States government. Please remove one or more studies before adding more. YANTAI, China, Sept. 25, 2020 /PRNewswire/ -- Remegen Biosciences Co., Ltd. ("RemeGen") today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for disitamab vedotin (RC48), a novel humanized anti-HER2 antibody drug conjugate (ADC), for the second-line treatment of patients with HER2 positive locally advanced or metastatic urothelial cancer .