This is a multicenter, single arm, prospective, open-label phase II trial investigating the clinical activity triplet regimen consisting of a combination of chemotherapy (gemcitabine/cisplatin) + trastuzumab + pembrolizumab as first-line treatment for cholangiocarcinoma and gallbladder cancer patients.
Patients suffering from previously untreated HER2 (human epidermal growth factor receptor 2) positive, unresectable cholangiocarcinoma and gallbladder cancer will be included in the study and are scheduled to receive triplet regimen consisting of a combination of pembrolizumab, trastuzumab and gemcitabine/cisplatin (GemCis).

开始日期2024-04-17

申办/合作机构

MSD Sharp & Dohme GmbH

DRKS00032606 / RecruitingN/A

A cross-sectional study on HPV vaccination in German women undergoing excisional CIN therapy and the impact of reimbursement on the acceptance (HPV vacCINe study) - HPV vacCINe study

开始日期2023-11-08

申办/合作机构

MSD Sharp & Dohme GmbH

DRKS00025510 / RecruitingN/A

HPV knowledge and acceptance of HPV vaccination among Men who have Sex with Men (MSM) in Germany: A cross-sectional study - HPV Study

开始日期2023-10-11

申办/合作机构

MSD Sharp & Dohme GmbH

100 项与 MSD Sharp & Dohme GmbH 相关的临床结果

登录后查看更多信息

0 项与 MSD Sharp & Dohme GmbH 相关的专利（医药）

登录后查看更多信息

127

项与 MSD Sharp & Dohme GmbH 相关的文献（医药）

2024-09-01·European Journal of Obstetrics & Gynecology and Reproductive Biology

Treatment characteristics, HPV genotype distribution and risk of subsequent disease among women with high-grade cervical intraepithelial neoplasia in Europe: A systematic literature review

Review

作者: Reuschenbach, Miriam ; Ghelardi, Alessandro ; Valente, Stefano ; Dhawan, Arju ; Takyar, Jitender ; Sabale, Ugne ; Nowakowski, Andrzej ; Hall, Adam ; Del Pino, Marta ; Agrawal, Neha

INTRODUCTIONHigh-grade cervical intraepithelial neoplasia (CIN), a premalignant lesion of the uterine cervix, is caused by persistent Human Papillomavirus (HPV) infection. CIN can be identified through screening programs and high-grade CIN is usually treated by ablation or excision. This study aimed to summarize the clinical management and outcomes among women with high-grade CIN in Europe.METHODSA systematic literature review was conducted to identify treatment methods and their frequency of use, report HPV genotype prevalence and distribution and summarize patterns for subsequent lesions after primary treatment, among women with high-grade CIN in Europe. Embase®, MEDLINE® and Cochrane databases were searched (1st January 2012 to 30th August 2022), along with relevant conference proceedings (2018-2022), inclusive. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) compliant methodology was adopted. Eligibility criteria included non-immunosuppressed female patients with CIN2+ from Europe (published in English).RESULTSIn total, n = 55 studies were included. CIN excisional therapy was the most received treatment approach (15.8-100 %, loop electrosurgical excision procedure/large loop excision of the transformation zone most common), followed by ablative therapies (1-43.3 %, cold coagulation most common). Other approaches included 'wait and watch' (4.8-52.6 %) and hysterectomy (4.8-16.2 %). HPV positivity rates ranged from 67.8-100 % pre-conization and 4.7-32.8 % post-conization. The most prevalent HPV genotypes reported (both pre- and post-treatment) were HPV16 and HPV18. In patients who received excisional or ablative procedures subsequent CIN was most frequently diagnosed ≤6 months after treatment. The overall rate of subsequent CIN reported was 0.5-20.9 %.CONCLUSIONConization and ablation were the most common techniques, however, these procedures were associated with sub-optimal outcomes. Close clinical follow-up is important due to the risk of subsequent CIN or invasive cancer. This review serves as a reference point for the comparison of future treatment patterns as they evolve across Europe, following improved implementation of prophylactic HPV vaccination and screening.

2024-04-01·Journal of Clinical Pathology

Comparison of assessment of programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer biopsies and surgical specimens

Article

作者: Roth, Wilfried ; Ballke, Simone ; Noske, Aurelia ; Steiger, Katja ; Oettler, Dirk ; Kiechle, Marion ; Weichert, Wilko

AimsProgrammed death-ligand 1 (PD-L1) status in triple-negative breast cancer (TNBC) is important for immune checkpoint inhibitor therapies but may vary between different immunohistochemical assays, scorings and the type of specimen used for analysis.MethodsWe compared the analytical concordance of three clinically relevant PD-L1 assays (VENTANA SP142, VENTANA SP263 and DAKO 22C3 pharmDx) assessing immune cell score (IC), tumour proportion score and combined positive score (CPS) in preoperative biopsies and resection specimens of primary TNBC. PD-L1 expression was scored on virtual whole slide images and compared with expression data from corresponding surgical specimens.ResultsThe mean PD-L1 positivity in TNBC biopsies defined as IC ≥1% and CPS ≥1 ranged between 11% and 61% with the lowest positivity for SP142 and highest for SP263. The corresponding surgical specimens showed overall higher positivity rates (53%–75%). When comparing biopsies with surgical specimens, the agreement for PD-L1 positivity with SP263 and 22C3 at IC score ≥1% and CPS ≥1 was fair (kappa 0.47–0.52) and poor for SP142 (kappa 0.15–0.19). Using CPS ≥10 cut-off, the agreement for SP263 was excellent (kappa 0.751) but poor for 22C3 (kappa 0.261). Spearman correlation coefficients ranged between 0.489 and 0.75 indicating a generally moderate to strong correlation between biopsies and surgical specimens for all assays and scores.ConclusionsWe demonstrate high accordance between biopsies and surgical specimens for SP263 and 22C3 scoring but less for SP142. Generally, biopsies are suitable for PD-L1 testing in TNBC but the appropriate assay, scoring and cut-off must be considered.

2024-02-01·Journal of Clinical Oncology

Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial.

作者: Clarke, Noel ; Arslan, Cagatay ; Hosius, Christian ; Armstrong, Andrew J. ; Joung, Jae Young ; Barnicle, Alan ; Sugimoto, Mikio ; McGuinness, David ; Procopio, Giuseppe ; Liu, Yu-Zhen ; Vianna, Karina ; del Rosario, Paula Michelle ; Shore, Neal D. ; Guedes, João Daniel Cardoso ; Schlürmann, Friederike ; Brown, Emma ; Saad, Fred ; Harrington, Elizabeth ; Oya, Mototsugu ; Mehra, Niven

165 Background: PROpel (NCT03732820) met its primary endpoint and showed a significant investigator-assessed radiographic progression-free survival (rPFS) benefit with O + A vs P + A in first-line mCRPC (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.001). At final prespecified analysis, median overall survival (OS) with O + A vs P + A was 42.1 vs 34.7 months (HR 0.81, 95% CI 0.67–1.00; P=0.0544). We report gene-by-gene efficacy of O + A vs P + A for pts from PROpel with a HRRm. Methods: PROpel was a Phase 3 randomized (1:1), double-blind trial. Pts were enrolled irrespective of biomarker status and received O (300 mg twice daily [bid]) or P, plus A (1000 mg once daily) and prednisone/prednisolone (5 mg bid). rPFS by investigator assessment was the primary endpoint (data cutoff [DCO]: 7/30/2021). OS was a key secondary endpoint (DCO: 10/12/2022). Following randomization and before primary analysis, HRRm status was assessed by tumor tissue (FoundationOne CDx) and ctDNA (FoundationOne Liquid CDx) tests and is reported using aggregated results from both tests. Genes assessed were ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L. HR and CIs are not reported in subgroups with <5 events in either arm for both rPFS and OS. Results: 28.4% pts had an HRRm.For most pts with a single gene HRRm, there was a lower proportion of rPFS events and deaths in the O + A arm relative to the P + A arm (Table). The most prevalent gene mutations were BRCA2, ATM and CDK12; HRs for rPFS and OS numerically favored O + A (rPFS: BRCA2, HR 0.20, 95% CI 0.08–0.44; ATM, HR 0.55, 95% CI 0.20–1.38; CDK12, HR 0.51, 95% CI 0.20–1.18. OS: BRCA2, HR 0.20, 95% CI 0.07–0.48; ATM, HR 0.79, 95% CI 0.33–1.77; CDK12, HR 0.57, 95% CI 0.24–1.27). Conclusions: BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820 . [Table: see text]

项与 MSD Sharp & Dohme GmbH 相关的新闻（医药）

2022-03-04

·BioSpace

Genome and Company announces Clinical Trial Collaboration with MSD to evaluate 'GEN-001' in combination of KEYTRUDA® (pembrolizumab) in phase 2 clinical trial in biliary tract cancer patients

Genome and Company (KOSDAQ: 314130, CEO∙CTO: Jisoo Pae∙Hansoo Park), a leading global microbiome anti-cancer drug development company, announced it has entered into a first Clinical Trial Collaboration and Supply Agreement (CTCSA) with MSD (a tradename of Merck & Co., Inc., Kenilworth, N.J., USA). Upon the execution of the agreement, Genome and Company will conduct a phase 2 clinical trial to evaluate the safety and efficacy of its immuno-oncology microbiome therapeutic, 'GEN-001', in combination with MSD's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with biliary tract cancer. Genome and Company will be the sponsor of the clinical trial and MSD will supply KEYTRUDA®. 'GEN-001' is an orally administered immuno-oncology microbiome therapeutic candidate consisting of Lactococcus lactis (L. lactis), a single live bacterial strain isolated from a healthy human. Biliary tract cancer is one of the carcinomas associated with a poor prognosis after diagnosis, limited treatment options and five-year survival rate of only 5 to 15%. According to the findings in the MDPI Cancers 2021, an SCI academic journal, the infiltrations of immune cells around cancer cells were observed in 70% of biliary tract cancer patients, also confirming the relationship between the immune cells and biliary tract cancer cells. Dr. Jisoo Pae, CEO of Genome and Company, said, "Genome and Company has established clinical trial collaborations to evaluate 'GEN-001' with both anti-PD-L1 and anti-PD-1 therapies through agreements with MSD, Merck KGaA, Darmstadt, Germany and Pfizer, which shows that the company is being recognized for its innovative technology by global immuno-oncology companies." He added, "Through this clinical trial collaboration, we look forward to evaluating the potential additive benefit of 'GEN-001' in combination with KEYTRUDA® as treatment for patients with biliary tract cancer." KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

帕博利珠单抗合作胆道癌小分子药物抗体

100 项与 MSD Sharp & Dohme GmbH 相关的药物交易

登录后查看更多信息

100 项与 MSD Sharp & Dohme GmbH 相关的转化医学

登录后查看更多信息