dc.contributor
Institut Català de la Salut
dc.contributor
[Curigliano G] Istituto Europeo di Oncologia, IRCCS, Milan, Italy. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. [Jimenez MM] Hospital General Universitario Gregorio Maranon, Madrid, Spain. [Shimizu T] National Cancer Center Hospital, Tokyo, Japan. [Keam B] Seoul National University Hospital, Seoul, South Korea. [Meric-Bernstam F] University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. [Rutten A] Sint-Augustinus Hospital, Antwerp, Belgium. [Garralda Cabanas E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Jiménez, Miguel Martín
dc.contributor.author
Shimizu, Toshio
dc.contributor.author
Keam, Bhumsuk
dc.contributor.author
Rutten, Annemie
dc.contributor.author
Curigliano, Giuseppe
dc.contributor.author
Meric-Bernstam, Funda
dc.contributor.author
GARRALDA, Elena
dc.date.accessioned
2025-10-25T05:37:38Z
dc.date.available
2025-10-25T05:37:38Z
dc.date.issued
2024-10-22T09:54:24Z
dc.date.issued
2024-10-22T09:54:24Z
dc.identifier
Curigliano G, Jimenez MM, Shimizu T, Keam B, Meric-Bernstam F, Rutten A, et al. A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies. ESMO Open. 2024 Aug;9(8):103643.
dc.identifier
https://hdl.handle.net/11351/12098
dc.identifier
10.1016/j.esmoop.2024.103643
dc.identifier
001286008800001
dc.identifier.uri
http://hdl.handle.net/11351/12098
dc.description.abstract
Tumors sòlids avançats
dc.description.abstract
Advanced solid tumors
dc.description.abstract
Tumores sólidos avanzados
dc.description.abstract
Background
LHC165 is a Toll-like receptor (TLR)-7 agonist that generates an effective tumor antigen-specific T-cell adaptive immune response as well as durable antitumor responses. We aimed to evaluate the safety, tolerability, efficacy, dose-limiting toxicities, and pharmacokinetics (PK) of LHC165 single agent (SA) ± spartalizumab [PDR001; anti-programmed cell death protein 1 (PD-1)] in adult patients with advanced solid tumors.
Materials and methods
In this phase I/Ib, open-label, dose-escalation/expansion study, patients received LHC165 SA 100-600 μg biweekly through intratumoral (IT) injection and LHC165 600 μg biweekly + spartalizumab 400 mg Q4W through intravenous (IV) infusion.
Results
Forty-five patients were enrolled: 21 patients received LHC165 SA, and 24 patients received LHC165 + spartalizumab. The median duration of exposure was 8 weeks (range 2-129 weeks). No maximum tolerated dose was reached. Recommended dose expansion was established as LHC165 600 μg biweekly as SA and in combination with spartalizumab 400 mg Q4W. The most common drug-related adverse events (AEs) were pyrexia (22.2%), pruritus (13.3%), chills (11.1%), and asthenia (4.4%). The only serious AE (SAE) suspected to be related to the study drug was grade 3 pancreatitis (n = 1). Across all tumor types, overall response rate and disease control were 6.7% and 17.8%, respectively. Overall median progression-free survival (PFS) and immune-related PFS was 1.7 months. LHC165 serum PK demonstrated an initial rapid release followed by a slower release due to continued release of LHC165 from the injection site.
Conclusions
LHC165 demonstrated acceptable safety and tolerability both as SA and in combination with spartalizumab, and evidence of limited antitumor activity was seen in adult patients with relapsed/refractory or metastatic solid tumors.
dc.description.abstract
This work was supported by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
dc.format
application/pdf
dc.relation
ESMO Open;9(8)
dc.relation
https://doi.org/10.1016/j.esmoop.2024.103643
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Anticossos monoclonals - Ús terapèutic
dc.subject
Càncer - Tractament
dc.subject
Quimioteràpia combinada
dc.subject
Avaluació de resultats (Assistència sanitària)
dc.subject
DISEASES::Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
dc.subject
ENFERMEDADES::neoplasias
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
dc.title
A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
