Purpose: RC48 contains the novel humanized anti-HER2 antibody hertuzumab conjugated to MMAE via a cleavable linker. A phase I study was initiated to evaluate the toxicity, MTD, PK, and antitumor activity of RC48 in patients with HER2-overexpressing locally advanced or metastatic solid carcinomas, particularly gastric cancer.
Patients And Methods: This was a 2-part phase I study. Successive cohorts of patients received escalating doses of RC48 (0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg). Dose expansion proceeded at the dose of 2.0 mg/kg Q2W. The efficacy and safety set included all patients who received at least one dose of RC48.
Results: Fifty-seven patients were enrolled, the MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D. RC48 was well tolerated, the most frequent grade 3 or worse TRAEs included neutropenia (19.3%), leukopenia (17.5%), hypoesthesia (14.0%), and increased conjugated blood bilirubin (8.8%). Four deaths occurred during the whole study, three of which were believed to be related to RC48. Overall, ORR and DCR were 21.0% (12/57) and 49.1% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+ and IHC3+, with ORRs of 35.7% (5/14), 20% (2/10), and 13.6% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efficacy, with ORR of 15.0% (3/20) and DCR of 45.0% (9/20).
Conclusion: RC48 was well tolerated and showed promising antitumor activity in HER2-positive solid tumors, including gastric cancer with HER2 IHC 2+/FISH- status.
Clinical Trial Information: NCT02881190.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205919 | PMC |
| http://dx.doi.org/10.1007/s10120-021-01168-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Concomitant formation of protocells and prebiotic compounds under a plausible early Earth atmosphere.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Crystallographic Studies, Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científica, Armilla 18100, Spain.
Revealing the origin of life and unambiguously detecting fossil remains of the earliest organisms are closely related aspects of the same scientific research. The synthesis of prebiotic molecular building blocks of life and the first compartmentalization into protocells have been considered two events apart in time, space, or both. We conducted lightning experiments in borosilicate reactors filled with a mixture of gases mimicking plausible geochemical conditions of early Earth.
View Article and Find Full Text PDFComparing Virtual Reality-Based and Traditional Physical Objective Structured Clinical Examination (OSCE) Stations for Clinical Competency Assessments: Randomized Controlled Trial.
J Med Internet Res
January 2025
Institute of Medical Teaching and Medical Education Research, University Hospital Würzburg, Würzburg, Germany.
Background: Objective structured clinical examinations (OSCEs) are a widely recognized and accepted method to assess clinical competencies but are often resource-intensive.
Objective: This study aimed to evaluate the feasibility and effectiveness of a virtual reality (VR)-based station (VRS) compared with a traditional physical station (PHS) in an already established curricular OSCE.
Methods: Fifth-year medical students participated in an OSCE consisting of 10 stations.
Smart Imitator: Learning from Imperfect Clinical Decisions.
J Am Med Inform Assoc
January 2025
Institute of Data Science, National University of Singapore, 117602, Singapore.
Objectives: This study introduces Smart Imitator (SI), a 2-phase reinforcement learning (RL) solution enhancing personalized treatment policies in healthcare, addressing challenges from imperfect clinician data and complex environments.
Materials And Methods: Smart Imitator's first phase uses adversarial cooperative imitation learning with a novel sample selection schema to categorize clinician policies from optimal to nonoptimal. The second phase creates a parameterized reward function to guide the learning of superior treatment policies through RL.
SIV Env RhmAbs + N-803 at ART initiation prolongs viral decay without disrupting reservoir establishment in SIV-infected infant macaques.
PLoS Pathog
January 2025
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.
View Article and Find Full Text PDFDonor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease.
Blood
January 2025
Stanford University Medical Center, Stanford, California, United States.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!