Hum Vaccin Immunother. 2025 Dec;21(1):2450878. doi: 10.1080/21645515.2025.2450878. Epub 2025 Jan 13.

ABSTRACT

As infants suffer significant morbidity and mortality due to norovirus-related acute gastroenteritis (AGE), we assessed four formulations of the bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in Panamanian and Colombian infants. 360 infants aged 6 weeks to 5 months were randomly allocated to 8 groups to receive three doses of HIL-214 or two doses of HIL-214 and one dose of placebo (Days 1, 56 and 112), where HIL-214 doses contained 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. Solicited injection-site and systemic adverse events (AE) were collected within 7 days after each dose, unsolicited AEs were collected within 28 days after each, and serious AEs throughout the study. Pan-Ig and histoblood group antigen-blocking antibodies (HBGA) were measured on Days 1, 56, 84, and 140. All formulations were well-tolerated causing mainly mild-to-moderate transient solicited AEs, most frequently local pain and irritability/fussiness, but no vaccine-related serious AEs. Two doses of each formulation induced high titers of high avidity Pan-Ig and also HBGA antibodies; a third dose increased titers against both antigens and the avidity of Pan-Ig antibodies against GII.4c but not against GI.1. Two and three doses of HIL-214 were well-tolerated and induced potent immune responses at 4-6 months of age supporting further clinical assessment to protect against norovirus-related AGE.

PMID:39803784 | DOI:10.1080/21645515.2025.2450878

J Lasers Med Sci. 2024 Nov 30;15:e60. doi: 10.34172/jlms.2024.60. eCollection 2024.

ABSTRACT

Introduction: Trastuzumab is now increasingly being used as a potent HER2 inhibitor in treating breast cancer, while acneiform rashes sometimes arise as skin-related side effects in patients undergoing treatment with HER2 inhibitors, and their specificity as drug-induced eruptions makes their management quite challenging. Pulsed dye laser (PDL) therapy has been utilized to treat a wide variety of vascular lesions, achieving excellent outcomes. Case Report: A 595 nm PDL was used to treat a 38-year-old woman suffering from an acneiform rash induced by trastuzumab as neoadjuvant therapy for breast cancer. One-half of the face received PDL treatment, while the other half served as the control. Conclusion: After just one PDL treatment, the skin lesion demonstrated a remarkable improvement, with a significant reduction in erythematous papules and inflammatory pustules, as well as an improvement in skin thickening. PDL therapy might offer an effective alternative for managing acneiform rashes induced by trastuzumab.

PMID:39802912 | PMC:PMC11725034 | DOI:10.34172/jlms.2024.60

Ceska Gynekol. 2024;89(6):501-503. doi: 10.48095/cccg2024501.

ABSTRACT

Estrogens are key hormones that play a vital role in the physiology of the reproductive system in women. However, their therapeutic use in hormonal treatment, contraception, and the treatment of hormone-dependent diseases may be associated with a number of side effects, especially on the liver. This article focuses on the mechanisms of action of estrogens and their potential hepatotoxic effects, as well as risk factors and possible differences between representatives.

PMID:39800550 | DOI:10.48095/cccg2024501

Eur J Hosp Pharm. 2025 Jan 12:ejhpharm-2024-004434. doi: 10.1136/ejhpharm-2024-004434. Online ahead of print.

NO ABSTRACT

PMID:39800473 | DOI:10.1136/ejhpharm-2024-004434

J Prev Alzheimers Dis. 2025 Jan;12(1):100002. doi: 10.1016/j.tjpad.2024.100002. Epub 2025 Jan 1.

ABSTRACT

BACKGROUND: Investigators conducting clinical trials have an ethical, scientific, and regulatory obligation to protect the safety of trial participants. Traditionally, safety monitoring includes manual review and coding of adverse event data by expert clinicians.

OBJECTIVES: Our study explores the use of natural language processing (NLP) and artificial intelligence (AI) methods to streamline and standardize clinician coding of adverse event data in Alzheimer's disease (AD) clinical trials.

DESIGN: Our quantitative retrospective study aimed to develop a gold standard AD adverse event data set, evaluate the predictive performance of NLP-based models to classify adverse events, and determine whether automated coding is more efficient, accurate, reliable, and consistent than clinician coding.

SETTING: Our study was conducted at the University of Southern California's Alzheimer's Therapeutic Research Institute (ATRI). ATRI serves as the clinical and data coordinating center for the Alzheimer's Clinical Trial Consortium (ACTC).

PARTICIPANTS: We collected demographic and adverse event data from eight completed clinical trials in participants (n=1920) with symptomatic AD conducted between 2005 and 2020.

MEASUREMENTS: Original expert clinician-confirmed codes were used for all model performance comparisons. F1 score was used as the primary model selection metric. Final classifier performance was evaluated using predictive accuracy. Clinician effort was measured in time to code, review, and confirm coded adverse events.

RESULTS: In a sample of 1000 adverse events, AI-based AE coding achieved higher accuracy (∼20% increase in accuracy) and was more cost-effective (∼80% cost reduction) than traditional clinician coding.

CONCLUSIONS: Our study results demonstrate how approaches that effectively combine AI and human expertise can improve the efficiency and quality of adverse event coding and clinical trial safety monitoring.

PMID:39800465 | DOI:10.1016/j.tjpad.2024.100002

J Emerg Nurs. 2025 Jan;51(1):20-26. doi: 10.1016/j.jen.2024.08.005.

ABSTRACT

Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the rapid onset of nonfollicular, sterile pustules on an erythematous base, typically accompanied by fever (≥38 °C), neutrophilia (7.0 × 10⁹/L), and characteristic histopathological features. This case report presents the first documented instance of acute generalized exanthematous pustulosis after hyaluronic acid viscosupplementation. A 61-year-old female developed a pruritic, erythematous rash that rapidly evolved into generalized erythroderma with systemic manifestations after receiving intra-articular hyaluronic acid injections for knee osteoarthritis. Initial physical examination and diagnostic workup, including biopsy and blood tests, were performed to exclude other differential diagnoses such as generalized pustular psoriasis, subcorneal pustular dermatosis, and immunoglobulin A pemphigus. The temporal association with hyaluronic acid injections and the patient's positive response to treatment with systemic corticosteroids and antihistamines supported the definitive diagnosis of drug-induced acute generalized exanthematous pustulosis. The patient was managed with the withdrawal of the offending agent, and supportive care was provided. She did not require rehabilitation and experienced no adverse events during the recovery period. Follow-up visits confirmed the absence of recurrence and complete resolution of symptoms, with no lasting sequelae. This case underscores the importance of recognizing acute generalized exanthematous pustulosis' acute manifestations and potential triggers, even with treatments generally considered safe. ED personnel, including advanced practice registered nurses and other clinicians, must include acute generalized exanthematous pustulosis in their differential diagnoses of severe cutaneous disorders to initiate prompt and appropriate management. The development of atrial fibrillation during hospitalization in this patient raises questions about the systemic effects of acute generalized exanthematous pustulosis, suggesting an area for further research. Early detection and treatment of acute generalized exanthematous pustulosis are crucial for favorable outcomes, illustrating the vital role ED personnel play in managing this condition. Awareness of rare triggers such as hyaluronic acid is essential for preventing and effectively treating such severe adverse reactions.

PMID:39800444 | DOI:10.1016/j.jen.2024.08.005

J Immunother Cancer. 2025 Jan 11;13(1):e010565. doi: 10.1136/jitc-2024-010565.

ABSTRACT

BACKGROUND: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG4-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

METHODS: SL-172154 was administered intravenously at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg. Dose escalation followed a modified toxicity probability interval-2 design. Objectives included evaluation of safety, dose-limiting toxicity, recommended phase II dose, pharmacokinetic (PK) and pharmacodynamic (PD) parameters, and antitumor activity.

RESULTS: 27 patients (median age 66 years (range, 33-85); median of 4 prior systemic therapies (range, 2-9)) with ovarian (70%), fallopian tube (15%), or primary peritoneal (15%) cancer received SL-172154. Treatment-emergent adverse events (TEAEs) were reported for 27 patients (100%), with 24 (88.9%) having a drug-related TEAE and infusion-related reactions being the most common. 12 patients (44.4%) had grade 3/4 TEAEs, and half of these patients (22.2%) had a drug-related grade 3/4 TEAE. There were no fatal adverse events, and no TEAEs led to drug discontinuation. SL-172154 Cmax and area under the curve increased with dose with greater than proportional exposure noted at 3.0 and 10.0 mg/kg. CD47 and CD40 target engagement on CD4+ T cells and B cells, respectively, approached 100% by 3.0 mg/kg. Dose-dependent responses in multiple cytokines (eg, interleukin 12 (IL-12), IP-10) approached a plateau at ≥3.0 mg/kg. Paired tumor biopsies demonstrated a shift in macrophages from an M2- to an M1-dominant phenotype and increased infiltration of CD8 T cells. PK/PD modeling showed near maximal margination of B cells and a dose-dependent production of IL-12 nearing a plateau at >3.0 mg/kg. The best response was stable disease in 6/27 (22%) patients.

CONCLUSIONS: SL-172154 was tolerable as monotherapy and induced, dose-dependent, and cyclical immune cell activation, increases in multiple serum cytokines, and trafficking of CD40-positive B cells and monocytes following each infusion. The safety, PK, and PD activity support 3.0 mg/kg as a safe and pharmacologically active dose.

TRIAL REGISTRATION NUMBER: NCT04406623.

PMID:39800375 | DOI:10.1136/jitc-2024-010565

Eur J Hosp Pharm. 2024 Dec 16:ejhpharm-2024-004429. doi: 10.1136/ejhpharm-2024-004429. Online ahead of print.

NO ABSTRACT

PMID:39797685 | DOI:10.1136/ejhpharm-2024-004429

Drug Ther Bull. 2024 Dec 22:dtb-2024-000070. doi: 10.1136/dtb.2024.000070. Online ahead of print.

NO ABSTRACT

PMID:39797682 | DOI:10.1136/dtb.2024.000070

Drug Ther Bull. 2024 Dec 22:dtb-2024-000069. doi: 10.1136/dtb.2024.000069. Online ahead of print.

NO ABSTRACT

PMID:39797681 | DOI:10.1136/dtb.2024.000069

Drug Ther Bull. 2024 Dec 22:dtb-2024-000068. doi: 10.1136/dtb.2024.000068. Online ahead of print.

NO ABSTRACT

PMID:39797680 | DOI:10.1136/dtb.2024.000068

Cancers (Basel). 2024 Dec 29;17(1):76. doi: 10.3390/cancers17010076.

ABSTRACT

Cancer immunotherapy, particularly immune checkpoint inhibitors, has positively impacted oncological treatments. Despite its effectiveness, immunotherapy is associated with immune-related adverse events (irAEs) that can affect any organ, including the liver. Hepatotoxicity primarily manifests as immune-related hepatitis and, less frequently, cholangitis. Several risk factors, such as pre-existing autoimmune and liver diseases, the type of immunotherapy, and combination regimens, play a role in immune-related hepatotoxicity (irH), although reliable predictive markers or models are still lacking. The severity of irH ranges from mild to severe cases, up to, in rare instances, acute liver failure. Management strategies require regular monitoring for early diagnosis and interventions, encompassing strict monitoring for mild cases to the permanent suspension of immunotherapy for severe forms. Corticosteroids are the backbone of treatment in moderate and high-grade damage, alone or in combination with additional immunosuppressive drugs for resistant or refractory cases. Given the relatively low number of events and the lack of dedicated prospective studies, much uncertainty remains about the optimal management of irH, especially in the most severe cases. This review presents the main features of irH, focusing on injury patterns and mechanisms, and provides an overview of the management landscape, from standard care to the latest evidence.

PMID:39796705 | DOI:10.3390/cancers17010076

Reg Anesth Pain Med. 2025 Jan 9:rapm-2024-106304. doi: 10.1136/rapm-2024-106304. Online ahead of print.

NO ABSTRACT

PMID:39793993 | DOI:10.1136/rapm-2024-106304

Eur J Cancer. 2024 Nov 16;216:115122. doi: 10.1016/j.ejca.2024.115122. Online ahead of print.

ABSTRACT

PURPOSE: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

METHODS: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles. Safety assessments included the nature of dose-limiting toxicities (DLTs) and the incidence and severity of adverse events (AEs) and serious AEs. The PK profile of MAK683 was assessed in sequential blood samples of cycles 1-6, and pharmacodynamic profiles were measured by H3K27me3 changes from baseline.

RESULTS: Overall, 139 patients (clear cell carcinoma of the ovary [CCCO], 9 [6.5%]; castration-resistant prostate cancer [CRPC], 22 [15.8 %]; diffuse large B-cell lymphoma [DLBCL], 31 [22.3%]; epithelioid sarcoma [ES], 17 [12.2 %]; gastric cancer [GC], 37 [26.6 %]; nasopharyngeal carcinoma [NPC], 17 [12.2 %]; SWI/SNF-mutated sarcoma, 6 [4.3 %]) received MAK683. Median duration of exposure was 57 days (range: 4-1006). Fifteen patients experienced 22 DLTs including thrombocytopenia (4.9 %) and febrile neutropenia (3.3 %). MAK683-related AEs were reported in 98 patients (70.5 %); 43 patients had grade 3/4 drug-related AEs, including neutropenia, thrombocytopenia, and anemia. MAK683 was quickly absorbed, with peak plasma concentrations ranging from 0.975 to 4.08 h. Median progression-free survival was 1.9 months (90 % confidence interval [CI]: 1.8-2.3), and overall response rate was 5.8 % (90 % CI: 2.52-11.03 %). Clinical activity was observed in patients with advanced DLBCL and ES.

CONCLUSION: Overall, MAK683 treatment was well tolerated, and clinical activity was observed in patients with advanced DLBCL and ES.

CLINICAL TRIAL INFORMATION: NCT02900651.

PMID:39793445 | DOI:10.1016/j.ejca.2024.115122

HCA Healthc J Med. 2024 Dec 1;5(6):739-743. doi: 10.36518/2689-0216.1738. eCollection 2024.

ABSTRACT

BACKGROUND: Nitrofurantoin is a prevalent antibiotic used to treat urinary tract infections. Despite nitrofurantoin's general safety, it can cause serious side effects, including acute pulmonary toxicity, fulminant hepatitis, and severe systemic inflammatory responses, which may mimic conditions such as ischemia and infection. However, reports of acute systemic inflammatory response syndrome after nitrofurantoin ingestion are uncommon in medical literature.

CASE PRESENTATION: This case describes a severe systemic inflammatory response syndrome in an 85-year-old woman presenting with hypoxia, altered mental status, and profound leukocytosis after exposure to a single dose of nitrofurantoin.

CONCLUSION: Herein we report on a patient with suspected bacteremia and urosepsis. Who was treated with broad-spectrum antibiotics. However, the antibiotic used to treat the patient's urinary tract infection caused an altered mental status and systemic inflammatory response. Therefore, it is crucial for clinicians to consider iatrogenic and medication-induced etiologies for altered mental status.

PMID:39790693 | PMC:PMC11708924 | DOI:10.36518/2689-0216.1738

J Transl Med. 2025 Jan 9;23(1):37. doi: 10.1186/s12967-024-05985-z.

ABSTRACT

BACKGROUND: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.

METHODS: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary endpoints were safety and to determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs). Pharmacokinetics and anti-tumor efficacy of GQ1001 were assessed. The plasma concentration of free DM1, the payload of GQ1001, was quantitated.

RESULTS: A total of 32 patients were enrolled, predominantly in breast (9), gastric or gastro-esophageal junction (9) and salivary gland cancer (4). Median number of prior-line of therapies was 3 (0-11) and 37.5% patients received ≥ 2 lines of anti-HER2 therapies. No DLT was observed during dose escalation. MTD was not reached and dose recommended for dose expansion (DRDE) was determined as 8.4 mg/kg. Grade ≥ 3 treatment-related adverse events rate was 28.1% (9/32) and platelet count decreased (4/32, 12.5%) was the most common one. No drug-related death was observed. Objective response rate and disease control rate of 15 evaluable patients in 7.2 mg/kg and 8.4 mg/kg cohorts were 40.0% (6/15) and 60.0% (9/15). Pharmacokinetics analysis showed low exposure and accumulation of free DM1 in circulation.

CONCLUSION: GQ1001 is well tolerated and shows promising efficacy in previously treated HER2-positive advanced solid tumors. DRDE was determined as 8.4 mg/kg for following trials. Trial registration NCT, NCT04450732, Registered 23 June 2020, https://clinicaltrials.gov/study/NCT04450732.

PMID:39789619 | DOI:10.1186/s12967-024-05985-z

Sci Rep. 2025 Jan 9;15(1):1455. doi: 10.1038/s41598-025-85681-0.

ABSTRACT

Drug-induced eosinophilic pneumonia (EP) is an uncommon adverse drug reaction. Many drugs have been reported to cause EP, the evidence mainly being in the form of case reports/case series. This study aims to conduct an exploratory analysis of the United States Food and Drug Administration adverse event reporting system (FAERS) database to identify previously unknown drugs that can cause EP and supplement the available evidence for known culprit drugs. A retrospective case-noncase study was conducted using individual case safety reports (ICSRs) reported to the US FAERS from the first quarter of 2004 to the second quarter of 2024. Cases of potentially drug-induced EP were identified using OpenVigil application by conducting a narrow and broad scope search using the Medical Dictionary of Regulatory Activities preferred terms. A base list of drugs described in select literature to have caused EP was used to categorize known and unknown drugs. A disproportionality analysis was performed, with a reporting odds ratio > 2, lower end of the 95% confidence interval > 1, and a minimum of 3 reported cases considered a signal of disproportionate reporting (SDR). During the study period, 8,702,548 individual case safety reports (ICSRs) were submitted to the FAERS. Of these, 855 ICSRs using the narrow scope search and 1411 ICSRs using the broad scope search reported EP. The three most commonly reported drugs with an SDR for EP using the narrow scope search were daptomycin, naltrexone, and prednisone. The most common indications for the use of the drugs were infections, immunological conditions, asthma, and central nervous system disorders. In total, there were 45 drugs with an SDR but no supporting literature evidence available. The number of drugs implicated in causing EP has increased over the years. Several antimicrobial agents, followed by drugs affecting the central nervous system and anticancer drugs, including monoclonal antibodies, can produce EP. The list of suspected drugs identified in this study, especially those with SDR and literature evidence, should be strongly considered as a possible cause in patients presenting with pneumonia not explained otherwise.

PMID:39789288 | DOI:10.1038/s41598-025-85681-0

Eur J Hosp Pharm. 2025 Jan 9:ejhpharm-2024-004353. doi: 10.1136/ejhpharm-2024-004353. Online ahead of print.

ABSTRACT

BACKGROUND: Tachyphylaxis is the rapid development of drug tolerance following repeated administration.

OBJECTIVES: To evaluate the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) data for drugs significantly associated with tachyphylaxis using disproportionality analysis.

METHODS: Disproportionality analysis was used for detecting safety signals for identifying drugs associated with tachyphylaxis. Frequentist and Bayesian statistical methods were employed to detect signals, identifying anesthetics, immunosuppressants, antineoplastics, and psychoactive drugs with positive associations.

RESULTS: Data from 29,153,222 reports between 2004 and 2024 were examined, and 242 reports of tachyphylaxis included. Tachyphylaxis was observed with corticosteroids, opioids, antihistamines, psycholeptics, nitroglycerin, antineoplastics, immunosuppressants, sympathomimetics, psychoanaleptics and psycholeptics that are well documented. Tachyphylaxis was also observed with propofol, cisatracurium, oxcarbazepine, and cabergoline emphasizing the need for further investigation. Hospitalization was reported in 16.9% of cases, with 5% leading to disability and 2.5% resulting in death.

CONCLUSION: While this study provides valuable insights into drug-related tachyphylaxis, limitations such as underreporting and lack of detailed clinical context exist. Future research should focus on understanding underlying mechanisms and developing strategies to mitigate tachyphylaxis in long-term treatments.

PMID:39788698 | DOI:10.1136/ejhpharm-2024-004353

Lancet Oncol. 2025 Jan 6:S1470-2045(24)00636-3. doi: 10.1016/S1470-2045(24)00636-3. Online ahead of print.

ABSTRACT

BACKGROUND: CMG901 is a novel first-in-class antibody-drug conjugate with a humanised anticlaudin 18.2 antibody linked to microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the antitumour activity and safety of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer and other solid tumours.

METHODS: KYM901 is a multicentre, open-label, single-arm, phase 1 trial consisting of dose-escalation and dose-expansion stages. Patients with advanced solid tumours, including gastric or gastro-oesophageal junction and pancreatic cancers, were recruited from 31 hospital sites in China. Eligible patients were aged 18 years or older, were refractory to standard therapy or had no available standard-of-care regimen, and had an Eastern Cooperative Oncology Group performance status score of 0-1, a life expectancy of at least 3 months, and at least one measurable lesion. Patients received intravenous CMG901 every 3 weeks (0·3-3·4 mg/kg in dose escalation and 2·2-3·0 mg/kg in dose expansion) until disease progression, unacceptable toxic effects, initiation of new antitumour therapy, study withdrawal, or death. Primary endpoints were adverse events and dose-limiting toxic effects in the dose-escalation phase, and objective response rate and recommended phase 2 dose in the dose-expansion phase. Confirmed objective response was defined as a partial or complete response that was verified by follow-up imaging at least 4 weeks after the initial assessment. Safety was assessed in all patients who received at least one dose of CMG901 with at least one post-dose safety evaluation. Antitumour activity was assessed in all patients who received at least one dose of CMG901 (full analysis set) and in all CMG901-treated patients with at least one post-dose imaging evaluation and no major protocol deviations (efficacy analysis set). Dose-expansion data for patients with pancreatic cancer will be published separately. Due to small sample sizes, results in patients with other solid tumours (n=2) are not planned for publication. This ongoing trial is registered with ClinicalTrials.gov, NCT04805307.

FINDINGS: Between Dec 24, 2020, and Feb 23, 2023, 27 patients were enrolled in the dose-escalation phase (median age 57·0 years [IQR 48·0-63·0]; 14 [52%] male, 13 [48%] female) and 107 patients with gastric or gastro-oesophageal junction cancer in the dose-expansion phase (median age 56·0 years [44·0-64·0]; 57 [53%] male, 50 [47%] female). As of Feb 24, 2024, one dose-limiting toxic effect (grade 3 pancreatitis) occurred at 2·2 mg/kg, and the maximum tolerated dose was not reached in the dose-escalation phase. All 27 patients reported at least one treatment-emergent adverse event, most frequently vomiting (19 [70%]), decreased appetite (16 [59%]), proteinuria (16 [59%]), and anaemia (15 [56%]), and five (19%) had drug-related grade 3 or worse treatment-emergent adverse events. In 107 patients, grade 3 or worse treatment-emergent adverse events occurred in 73 (68%) patients and serious adverse events occurred in 54 (50%) patients in dose expansion. The most common grade 3-4 adverse events were neutrophil count decreased (22 [21%]), anaemia (15 [14%]), and vomiting (11 [10%]). One treatment-related death was reported. At median follow-up of 9·0 months (IQR 4·4-12·9), among 113 patients with gastric or gastro-oesophageal junction cancer in the 2·2-3·0 mg/kg cohort full analysis set across both the dose-escalation and dose-expansion phases, the confirmed objective response rate was 28% (95% CI 20-38; 32 of 113 patients). In the 109 patients included in the efficacy analysis set, the confirmed objective response rate was 29% (95% CI 21-39; 32 of 109 patients). Based on overall safety, activity, and pharmacokinetics of CMG901, 2·2 mg/kg was the proposed recommended phase 2 dose.

INTERPRETATION: CMG901 showed a manageable safety profile and had promising antitumour activity in patients with advanced gastric or gastro-oesophageal junction cancer.

FUNDING: KYM Biosciences.

PMID:39788133 | DOI:10.1016/S1470-2045(24)00636-3

Virology. 2025 Jan 3;603:110391. doi: 10.1016/j.virol.2025.110391. Online ahead of print.

ABSTRACT

The integration of nanotechnology into antiretroviral drug delivery systems presents a promising avenue to address challenges posed by long-term antiretroviral therapies (ARTs), including poor bioavailability, drug-induced toxicity, and resistance. These limitations impact the therapeutic effectiveness and quality of life for individuals living with HIV. Nanodrug delivery systems, particularly nanoemulsions, have demonstrated potential in improving drug solubility, enhancing bioavailability, and minimizing systemic toxicity. Moreover, nanodrug platforms can target viral reservoirs, potentially reducing the emergence of drug-resistant strains-a significant challenge in anti-HIV treatment. This study evaluates the biological efficacy of a rosemary oil-based nanoemulsion loaded with Nelfinavir (NFV) and Epigallocatechin Gallate (EGCG), which demonstrated HIV-1 suppression at sub-CC₅₀ concentrations across two distinct cellular systems. The synergistic interaction between NFV and EGCG was confirmed through cellular assays, enzymatic studies, and molecular interaction analysis. In vitro experiments revealed that the NE-NFV-EGCG nanoemulsion exhibited enhanced HIV-1 inhibitory activity compared to pure NFV, highlighting a promising therapeutic synergy. The findings suggest that EGCG could be a valuable adjunct in NFV-based regimens for HIV management. Molecular interaction studies further confirmed the nanoemulsion's inhibitory potential against the HIV-1 protease enzyme. This study marks a significant advancement in HIV-1 treatment by documenting, for the first time, the synergistic inhibitory activity of NFV and EGCG. The novel nanoformulation offers improved oral bioavailability, minimal side effects, and enhanced therapeutic outcomes. Future studies are needed to optimize the formulation for clinical applications, including sustained drug release and drug transport mechanisms.

PMID:39787774 | DOI:10.1016/j.virol.2025.110391