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Phase Ib/II trial of talimogene laherparepvec alone and with pembrolizumab in advanced solid tumors with liver metastases and hepatocellular carcinoma
Get PDFHepatocellular carcinoma; Liver metastasis; Solid tumorCarcinoma hepatocelular; Metástasis hepática; Tumor sólidoCarcinoma hepatocel·lular; Metàstasi hepàtica; Tumor sòlidBackground
Newer effective therapies are needed for patients with solid tumors with liver metastases and unresectable hepatocellular carcinoma (HCC).
Methods
Part 1 (dose exploration) evaluated intrahepatic talimogene laherparepvec (T-VEC) injection in group A (non-HCC liver metastases) and group B (HCC). Cohorts 1-4 received T-VEC monotherapy; cohorts 5 and 6 received T-VEC+pembrolizumab. Part 2 (dose expansion) evaluated intrahepatic or intratumoral T-VEC+pembrolizumab in non-HCC solid tumors. The primary endpoints were dose-limiting toxicities (DLTs) in part 1; objective response rate (ORR) per modified irRC-RECIST and safety in part 2.
Results
Part 1 enrolled 28 and 46 patients to receive T-VEC and T-VEC+pembrolizumab, respectively. Three patients reported DLTs (T-VEC, n = 2 grade 3 abdominal pain and aspartate transaminase increase; T-VEC+pembrolizumab, n = 1 grade 3 cholestatic hepatitis). ORR (secondary endpoint) with T-VEC was 0%; ORR (95% CI) with T-VEC+pembrolizumab was 8.3% (1.0, 27.0) for non-HCC and 13.6% (2.9, 34.9) for HCC. Part 2 enrolled 53 patients; ORR (95% CI) was 0% (0.0, 30.8)-20.0% (0.5, 71.6) across 5 tumor types, with 16.7% (95% CI: 3.6, 41.4) for triple-negative breast cancer with the largest sample size (n = 18). Safety findings were consistent with the therapies administered.
Conclusions
Limited efficacy across tumor types evaluated limit further evaluation of intrahepatic T-VEC+pembrolizumab in this patient population.
ClinicalTrials.gov Identifier
NCT02509507.Medical writing support was provided by Shubha Dastidar, PhD, CMPP (Cactus Life Sciences, part of Cactus Communications) and was funded by Amgen Inc. The study was sponsored and funded by Amgen Inc. This study is in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. This study was sponsored by Amgen Inc
Internal structure, reliability and cross-cultural validity of the Warwick-Edinburgh Mental Wellbeing Scale in three European populations
Get PDFCross-Sectional Studies; Data Interpretation, StatisticalBenestar mental; Escala de Warwick-Edimburg; Enquestes poblacionalsBienestar mental; Escala de Warwick-Edimburgo; Encuestas poblacionalesThe Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), a questionnaire designed for the assessment of mental well-being, is widely used in different countries and cultures worldwide. However, there is a lack of studies examining its metric performance and measurement invariance across countries.
This study aims to examine the internal structure, reliability and cross-country validity of the WEMWBS in three European populations.
WEMWBS data collected in 2016 from three representative population health surveys from an autonomous region in Spain (Catalonia) and two countries (Denmark and the UK) were used (n=13 940). The mean WEMWBS Scores were compared between populations. The internal consistency (ω coefficients), internal structure (confirmatory factor analyses (CFA) and bifactor exploratory structural equation models), reliability (item response theory models, item and test information functions), and cross-cultural comparability (multigroup CFA) of the WEMWBS were assessed.
Differences in mean scores observed between regions merit further study. The WEMWBS showed high internal consistency across countries (ω=0.942). The unidimensionality of the scale was confirmed overall and for each population. Evidence of reliability and of measurement invariance at the configural, scalar and metric levels was found.
The results support the use of the WEMWBS in different cultures to inform the understanding of population well-being in public health and its possible use as an outcome measure in clinical studies.The present work is funded by CIBER – Consorcio Centro de Investigación Biomédica en Red, Epidemiology and Public Health, ISCIII, Ministerio de Ciencia e Innovación (ESPI0521 Mental GPS), Instituto de Salud Carlos III and cofunded by the European Union (grant numbers PI23/00073; PI19/00109), ISCIII‐FSE+ (CP21/00078) MSERVET PMortier; Subdirecció General d'Addiccions, VIH, ITS i Hepatitis Víriques, Secretaria de Salut Pública, Departament de Salut, Generalitat de Catalunya“, the Medical Research Council (MRC) and Guy’s charity. This article represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South LondonPI23 and Maudsley NHS Foundation Trust and King’s College London. Departament de Recerca i Universitats, Generalitat de Catalunya (AGAUR 2021 SGR 00624)
Pla d'enquestes de percepció, experiència i satisfacció d'usuaris del CatSalut (PLAENSA): atenció hospitalària amb internament d'aguts
No full textEnquestes de satisfacció; Atenció hospitalària; Internament d'agutsEncuestas de satisfacción; Atención hospitalaria; Internamiento de agudosSatisfaction surveys; Hospital care; Internally of trebleLa novena edició de l’estudi de percepció, experiència i satisfacció amb el servei d’atenció hospitalària amb internament, dut a terme per la Unitat d’Avaluació i Experiència del Pacient en el marc del Pla d’enquestes de percepció, experiència i satisfacció dels usuaris del Servei Català de la Salut (CatSalut), ha mostrat que les persones que han utilitzat aquest servei durant l’any 2024 valoren la satisfacció amb l’atenció rebuda amb un 8,29 sobre 10 de mitjana. A més a més, de les persones que s’han entrevistat, un 88,8% ha respost que “Sí” a la pregunta: “Si poguéssiu triar, continuaríeu venint a aquest hospital?”. Les preguntes amb una major freqüència de respostes positives son: la “P8. Tracte personal de les infermeres i infermers” , amb un 95,4% de respostes positives, la “P21. Ajudar a controlar i millorar el dolor”, amb un 95,2% de respostes positives i “P19. Informació coherent”, amb un 94,9%. Aquest estudi compta amb 4.478 casos, procedents del registre d’activitat dels centres proveïdors. Durant aquesta edició de l’any 2024, s’ha utilitzat un qüestionari validat durant l’any 2022, que s’ha tornat a validar després de l’edició d’enguany. El treball de camp s’ha dut a terme entre l'11 i el 15 de març de l’any 2024, utilitzant un qüestionari web amb invitació per SMS
Diferencias en el perfil mutacional del linfoma T paniculítico y la paniculitis lúpica. Nueva serie de casos
Get PDFLinfoma de células T tipo paniculitis subcutánea; Lupus-paniculitis; Secuenciación de próxima generaciónSubcutaneous panniculitis-like T-cell lymphoma; Lupus panniculitis; Next-generation sequencingLimfoma de cèl·lules T tipus paniculitis subcutània; Lupus-paniculitis; Seqüenciació de pròxima generacióBackground
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed.
Objectives
The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP.
Materials and methods
We studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained.
Results
The mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes.
Conclusions
The mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.Introducción
El linfoma T paniculítico (LTP) es un linfoma de células T citotóxico poco frecuente, de comportamiento indolente, más frecuente en mujeres, relacionado con enfermedades autoinmunes, y cuyos antecedentes patogénicos aún no se conocen bien. Se asocia y se confunde histológicamente con la paniculitis lúpica (PL).
Objetivos
El objetivo de nuestro estudio fue identificar mutaciones implicadas en la patogénesis del LTP y de la PL.
Materiales y métodos
Se estudiaron 10 pacientes con LTP y 10 con PL mediante secuenciación masiva (con un panel de genes customizados) y pirosecuenciación dirigida. Se investigaron diferencias en la expresión genética mediante NanoString entre diferentes subgrupos moleculares encontrados. Se recopilaron datos clínicos y se correlacionaron con los datos moleculares obtenidos.
Resultados
El perfil mutacional del LTP y el de la LP son diferentes. El porcentaje de mutaciones encontradas en el subgrupo de LTP fue inferior al ya publicado en la literatura. Solo un paciente con LTP mostraba mutaciones en el gen HAVCR2. Curiosamente, el 40% de los LTP mostraron la variante patogénica TP53 (p.Pro72Arg) (P72R). Los pacientes con mutaciones en el gen HAVCR2 o con la variante TP53 (P72R) sufrían enfermedad sintomática, aunque ninguno desarrolló síndrome hemofagocítico (SPH). El estudio de NanoString identificó que las muestras con alteración de TP53 (P72R) se caracterizaban por una down-regulation de la vía de señalización del metabolismo y de una mayor expresión de los genes de las vías de señalización de CD28 y Treg si se comparaban con los casos negativos para TP53 (P72R). Además, el 30% de nuestros casos presentaban la misma mutación (T735C) en el gen modificador epigenético DNMT3A. Ninguno de los pacientes con PL mostró mutaciones en ninguno de los genes estudiados.
Conclusiones
Ampliamos el perfil mutacional del LTP, describiendo por primera vez la implicación de la variante patogénica TP53 (P72R) en este subgrupo de tumores. Además, sugerimos el posible papel de un fondo genético en el desarrollo de los LTP. La aparición de PL no parece seguir la misma vía patogénica que la de los LTP.This work was supported by grants from the Instituto de Salud Carlos III, from the Ministry of Science and Innovation of Spain, PI17/2172; ISCIII-MINECO-AES-FEDER. R.A.-A. is the recipient of PFIS predoctoral fellowship. L.T.-R. is funded by Marie Skłodowska-Curie Individual Fellowship (No. 882597). M.R.-M. is supported by CIBERONC (CB16/12/00291). P.M. has a Miguel Servet contract funded by the ISCIII (CP16/00116). L.d.l.F. was supported by the ISCIII contract CA18/00017
Challenges in implementing a total hip arthroplasty program in a developing country: Our experience at Monkole Hospital in the Democratic Republic of Congo
Get PDFPrótesis total de cadera; Osteonecrosis de cabeza femoral; ÁfricaTotal hip arthroplasty; Femoral head osteonecrosis; AfricaPròtesi total de maluc; Osteonecrosi de cap femoral; ÀfricaAntecedente y objetivos
La artroplastia total de cadera (ATC) es una cirugía efectiva para tratar la osteoartritis de cadera, pero su acceso es limitado en África subsahariana debido a múltiples desafíos. Este artículo describe la implantación de un programa de ATC en el Hospital Monkole de la República Democrática del Congo (RDC), centrándose en los desafíos técnicos y las complicaciones quirúrgicas. El objetivo es compartir nuestra experiencia para ayudar a otros profesionales y organizaciones en entornos similares.
Material y métodos
Se han realizado 8 campañas de cirugía de ATC entre julio del 2019 y febrero del 2023. La mayoría de los pacientes presentan necrosis de la cabeza femoral secundaria a anemia drepanocítica. Los datos demográficos, quirúrgicos, dificultades técnicos y complicaciones fueron recolectados de forma prospectiva y el seguimiento fue realizado por un traumatólogo local.
Resultados
Se han realizado 73 cirugías en 63 pacientes con una edad media de 34 años y un seguimiento medio de 24 meses. Se observaron 17 incidencias técnicas intraoperatorias. La tasa de complicaciones postoperatorias fue del 9,5% y 3 pacientes precisaron cirugía de revisión por complicaciones.
Conclusiones
El programa de ATC en el Hospital Monkole demuestra que es posible realizar cirugías complejas en países en desarrollo, y que es un procedimiento costo-efectivo que mejora la calidad de los pacientes. La formación de los cirujanos locales y la inversión en los recursos son claves para la sostenibilidad del programa y la mejora de la atención quirúrgica.Background and objectives
Total hip arthroplasty (THA) is an effective surgery for treating hip osteoarthritis, but access is limited in Sub-Saharan Africa due to multiple challenges. This article describes the implementation of a THA program at Monkole Hospital in the Democratic Republic of Congo, focusing on the technical challenges and surgical complications. The objective is to share our experience to assist other professionals and organizations in similar settings.
Materials and methods
Eight THA surgery campaigns were conducted between July 2019 and February 2023. Most patients presented with femoral head necrosis secondary to sickle cell anemia. Demographic and surgical data, technical difficulties, and complications were prospectively collected, and follow-up was conducted by a local orthopedic surgeon.
Results
Seventy-three surgeries were performed on 63 patients with a mean age of 34 years and an average follow-up of 24 months. Seventeen intraoperative technical incidents (23.2%) were observed. The postoperative complication rate was 9.5%, and three patients required revision surgery due to complications.
Conclusions
The THA program at Monkole Hospital demonstrates that it is feasible to perform complex surgeries in developing countries and that it is a cost-effective procedure that improves patients’ quality of life, provided there are adequate hospital infrastructures, team training, availability of implants, and ensured proper care and follow-up. Training local surgeons and investing in resources are key to the sustainability of the program and the improvement of surgical care
Plain language summary of quality of life in CheckMate 9ER: Cabozantinib plus nivolumab in advanced renal cell carcinoma
Get PDFMetastasis; Renal cell carcinoma; Targeted therapyMetàstasi; Carcinoma de cèl·lules renals; Teràpia dirigidaMetástasis; Carcinoma de células renales; Terapia dirigidaWhat is this summary about?
This is a plain language summary of an article about the quality-of-life analyses of the CheckMate 9ER study, originally published in the journal The Lancet Oncology.
The CheckMate 9ER study compared two different treatment options in people with advanced renal cell carcinoma (RCC), which is an advanced form of kidney cancer.
Investigators compared a newer drug combination, cabozantinib plus nivolumab (CaboNivo), with another drug called sunitinib. Sunitinib was the standard of care used to treat people with advanced RCC when the study was designed. The purpose of the study was to see whether people diagnosed with advanced RCC lived longer if they were treated with CaboNivo or sunitinib as their first treatment. Their quality of life while on treatment was also measured as part of the study.
To understand the effect of treatment on their quality of life, people completed two types of questionnaires at regular intervals during the study.
The first was the FACT Kidney Symptom Index (or FKSI-19) questionnaire, designed for people with kidney cancer. FKSI-19 asked questions about people's cancer symptoms and their side effects of cancer treatment, and how these impacted their quality of life. The second questionnaire was the EQ-5D-3L, designed for any person (with or without cancer). EQ-5D-3L asked people to rate five common aspects of health and their overall health.
The study also looked at how long it took for quality-of-life questionnaire ratings to worsen.
What are the key takeaways?
Results for both questionnaires suggested that quality of life was better for people in the CaboNivo group than those in the sunitinib group. People treated with CaboNivo were able to maintain their quality of life for longer than those treated with sunitinib.
What are the main conclusions reported by the researchers?
Overall, quality-of-life results from the CheckMate 9ER study showed that people treated with CaboNivo lived longer and were less bothered by the impact of their treatment than those treated with sunitinib.
Based on these results, CaboNivo is one of the standard-of-care treatments recommended first for people with advanced RCC.
Clinical Trial Registration: NCT03141177 (CheckMate 9ER) (ClinicalTrials.gov)This manuscript was funded by Ipsen. The manuscript was also reviewed and approved by Ipsen and Bristol Myers Squibb
Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status
Get PDFCàncer de mama; Línia germinal BRCACáncer de mama; Línea germinal BRCABreast cancer; Germline BRCAPurpose
To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene (BRCA1 v BRCA2) and the association of the timing of genetic testing (before v at diagnosis) with prognosis.
Methods
This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2, who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).
Results
Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor–negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]).
Conclusion
This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS
A virtual simulation study of the effects of laparotomy incision location and wound stiffness on abdominal wall mechanics
Get PDFAbdominal wall; Incision; LaparotomyParet abdominal; Incisió; LaparotomiaPared abdominal; Incisión; LaparotomiaIncisional hernia (IH) is a common complication of laparotomy surgical procedures, influenced by factors such as incision location and surgical wound (SW) tissue strength, and the intra-abdominal pressure (IAP) levels the patient is subject to. In this study we use finite element simulations to investigate how these factors affect the abdominal wall (AW) deformation and the stress distribution on the tissues. Comprehensive geometric models of the AW were generated for five laparotomy incisions, namely midline, paramedian, pararectus, transverse supraumbilical, and subcostal oblique. Finite element simulations for IAP values between 4 and 20 kPa and with the SW tissue strength ranging from very soft to very stiff were conducted using the code Aster open-source software. Simulations revealed that as a general rule laparotomy incisions significantly impact AW mechanics when the SW tissue is soft. In particular, AW mechanics is more sensitive to SW strength in vertical incisions (midline, paramedian, pararectus). The resulting change of the SW dimensions with increasing IAP was also investigated. Softening the SW tissue led to substantial volume increases of the vertical incisions for a given IAP level. In addition, we analyzed stress levels in the SW tissue as well as in the surrounding muscles. A very soft SW may induce the appearance of regions with very high stress levels in the surrounding muscle tissue, heightening their rupture risk. This effect was especially noticeable for the midline incision. On the overall, we found that when the SW tissue is too tender transverse supraumbilical and subcostal incisions present the lowest risk of tissue ruptures whereas the midline incision is the most vulnerable one and the paramedian and pararectus incisions stand midway. In summary, the results of the present simulation provide full support for the clinical guidelines’ recommendation to avoid midline incisions in abdominal surgeries whenever possible.T his project has been partially founded by AGAUR research group 2021SGR-00111: “ASCLEPIUS: Smart Technology for Smart Healthcare”
Genomic characterization of invasive Neisseria meningitidis in Spain (2011/12–2022/23): expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage
Get PDFNeisseria meningitidis; Antimicrobial susceptibility; Whole genome sequencingNeisseria meningitidis; Susceptibilidad antimicrobiana; Secuenciación del genoma completoNeisseria meningitidis; Susceptibilitat antimicrobiana; Seqüenciació del genoma completInvasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 Neisseria meningitidis isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12–2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.This work was supported by the “Instituto de Salud Carlos III” and cofinanced by the European Regional Development Fund (ERDF) grant number FIS PI21/00132, and by the “Centro de Investigación Biomédica en Red” (CIBER de Enfermedades Infecciosas) grant number CB21/13/00054
Safety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors
Get PDFAntitumor Activity; Solid tumorsActividad antitumoral; Tumores sólidosActivitat antitumoral; Tumors sòlidsPurpose: Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab were evaluated in two phase I studies.
Patients and methods: Adult patients with advanced solid tumors were administered intravenous RG6292, given every 3 weeks alone (study 1: NCT04158583, n = 76) or with 1,200 mg atezolizumab every 3 weeks (study 2: NCT04642365, n = 49). Both studies included dose escalation and expansion parts to determine the maximum tolerated dose and recommended phase II dose.
Results: RG6292 was well tolerated. Pruritus and rash were the most frequent adverse events and were manageable with supportive treatment. Serum RG6292 levels increased dose proportionally, independent of the atezolizumab combination. RG6292 induced a sustained dose-dependent depletion of peripheral Tregs with no apparent effect on other immune cells. Evidence of intratumoral Treg reduction (≥50% vs. baseline) was observed at RG6292 doses of 35 to 100 mg. The maximum tolerated dose was 165 mg every 3 weeks, and the recommended phase II dose was proposed as 70 mg every 3 weeks. Objective responses were limited to three partial responses in patients receiving RG6292 combined with atezolizumab.
Conclusions: RG6292 induced a dose-dependent peripheral blood and measurable intratumoral Treg depletion in concordance with the proposed mode of action; however, clinical efficacy as a single agent or combined with atezolizumab was insufficient to warrant further exploration in this population.
Significance: RG6292 (vopikitug) targets CD25 (IL-2Rα) and mediates regulatory T-cell depletion while not interfering with IL-2 signaling. Peripheral and intratumoral Treg depletion was shown in two phase I studies. However, RG6292 alone or in combination with atezolizumab was insufficient to reverse and rescue from established resistance mechanisms in solid tumors.F. Hoffmann-La Roche