Monoclonal Antibody Targeting Research Articles

A humanized monoclonal antibody attenuates fentanyl self-administration and reverses and prevents fentanyl-induced ventilatory depression in rhesus monkeys.

Medications for opioid use disorder (OUD) and overdose have been available for decades, yet nearly 70% of fatal drug overdoses in the United States are attributed to the opioid receptor agonist fentanyl and its analogs. There is a pressing need for more and better medications that reduce fentanyl use and prevent overdose. A humanized (h) monoclonal antibody (mAb) targeting fentanyl, hHY6-F9, was tested for attenuating intravenous fentanyl self-administration and reversing and preventing fentanyl-induced ventilatory depression in rhesus monkeys. A single administration of hHY6-F9 significantly decreased fentanyl, but not heroin or cocaine, self-administration. In some monkeys, fentanyl self-administration remained decreased for ~ 2 weeks. hHY6-F9 was as effective as 32µg/kg naloxone in reversing fentanyl-induced ventilatory depression, with a single administration protecting against fentanyl-induced ventilatory depression for 2-3 weeks. Moreover, pharmacokinetic analyses indicate that hHY6-F9 continued to sequester fentanyl in the serum for 2 weeks. This study demonstrates that hHY6-F9 selectively attenuates the positive reinforcing and ventilatory depressant effects of fentanyl, indicating its possible utility for preventing relapse and overdose.

Dupilumab for treatment of primary cutaneous amyloidosis in adults: two case reports and literature review

Lichenoid amyloidosis (LA), a subtype of primary cutaneous amyloidosis (PCA), is featured by intensely pruritic, hyperkeratotic papules which lacks standardized treatment. Dupilumab, a human monoclonal antibody targeting for interleukin (IL)-4/13 receptor α chain, is widely applied in type 2 inflammation diseases treatment. This article reported two cases of refractory LA successfully treated with dupilumab and reviewed publications reporting dupilumab treatment for PCA.

A phase II, randomized study of JMT101 in combination with irinotecan and SG001 versus regorafenib in patients with metastatic colorectal adenocarcinoma (mCRC).

TPS314 Background: Epidermal growth factor receptor (EGFR) inhibitorcombined withchemotherapy based on5-FU with oxaliplatin and irinotecanis the first-line treatment of wild-type RAS mCRC.JMT101 is a humanized monoclonal IgG1 antibody targeting EGFR. Previous trials showed that JMT101 monotherapy or in combination with chemotherapy had demonstrated a promising anti-tumor activity in advanced solid tumors with good safety profiles. EGFR inhibitor might have a synergetic effect with immunocheckpoint inhibitor (ICI) by activating innate and adaptive immune response. SG001 is a fully humanized and high-affinity immunoglobulin G4 monoclonal antibody that targets programmed death-1 (PD-1), which also had encouraging efficacy in advanced solid tumors. Therefore, EGFR antibody in combination with chemotherapy plus ICI is worthy exploration in patients with mCRC. Methods: This is a phase II, multicenter, open-label, two-part study. Part I is a safety run-in, followed by part II randomized treatment. Eligible patients are histologically confirmed mCRC without MSI-H/dMMR, wild-type RAS and BRAF, who progressed on at least 2 prior systemic therapy with chemotherapy based on 5-FU with oxaliplatin and irinotecan, with or without cetuximab and bevacizumab (both parts); no prior treatment with regorafenib, fruquintinib, or TAS-102 (part II). Safety run-in data will be analyzed after 3-6 patients have received JMT101 6 mg/kg plus irinotecan 180 mg/m 2 plus SG001 240 mg Q2W. Upon dose confirmation, 90 patients with mCRC will be randomized into three arms (1:1:1) to receive JMT101 plus irinotecan plus SG001, or JMT101 plus irinotecan, or regorafenib monotherapy. Primary endpoints include incidence of dose limiting toxicities (DLT) and adverse events (part I) and objective response rate (ORR) as per RECIST v1.1 by investigator (part II). Secondary endpoints include JMT101 and SG001 pharmacokinetic profile, antidrug antibodies (ADA) (both parts), disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS), as well as safety (part II). Prespecified goal for safety run-in part was met; randomized treatment part accrual began in February 2024. Clinical trial information: NCT06089330 .

A randomized phase II clinical trial evaluating the safety and efficacy of initial dose adjustment of zolbetuximab plus chemotherapy in patients with HER2-negative and CLDN18.2-positive unresectable advanced or recurrent gastric, gastroesophageal junction cancer or esophageal adenocarcinoma (GENTLE-Z).

TPS504 Background: Zolbetuximab, a monoclonal antibody targeting CLDN18.2, was recently approved in Japan for patients with HER2-negative/CLDN18.2-positive metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). On-target GI toxicities such as nausea and vomiting are commonly observed during first infusion, occasionally leading to early treatment discontinuation. Effective management of these toxicities is essential for the successful use of zolbetuximab in clinical practice. This study aims to assess whether omitting the loading dose in the first cycle can reduce zolbetuximab-related GI toxicities without compromise efficacy . Methods: GENTLE-Z is a prospective, open-label, multi-intuitional, randomized phase II trial designed to compare the safety and efficacy of fixed-dose of zolbetuximab without loading dose vs. the standard zolbetuximab dose in combination with first-line mFOLFOX6 or CAPOX for patients with HER2-negative/CLDN18.2-positive mGC/GEJC. Patients are randomly assigned (1:1) to receive either a fixed dose of zolbetuximab (400 mg/m 2 q2w or 600 mg/m 2 q3w) or standard zolbetuximab regimen (800 mg/m 2 loading dose followed by 400 mg/m 2 q2w or 600 mg/m 2 q3w) with chemotherapy. The primary endpoint is the vomit-free rate during cycle 1, and secondary endpoints include efficacy outcomes such as objective response rate, progression-free survival and overall survival. The sample size is set based on the hypothesis that omitting loading dose will improve the vomit-free rate from 50% to 75%. The planned sample size is 86 patients, with a one-sided alpha error of 5% and power of 75%, over an estimated enrollment period of 1.5 years. Enrollment has been ongoing since September 2024 across 55 sites in Japan. This trial is registered in Japan Registry of Clinical Trials (jRCTs031240347). Clinical trial information: jRCTs031240347.

Bifunctional anti-PD-L1/TGF-βRII agent SHR-1701 plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Survival results of a phase II trial.

411 Background: Recently, several clinical trials have demonstrated synergistic efficacy by combining immune checkpoint inhibitors (ICIs) with chemotherapy. However, only a subset of patients (pts) derived benefits. Combining ICIs with agents blocking immunosuppressive pathway may expand the clinical benefit of ICIs to more pts. Transforming growth factor β (TGF-β) participates in tumor immune escape. SHR-1701, a novel bifunctional fusion protein consisting of a monoclonal antibody targeting PD-L1 fused with the extracellular domain of TGF-β receptor II, was evaluated in a phase II trial (ChiCTR2000039909) to assess its efficacy and safety when combined with chemotherapy for pts with unresectable locally advanced, recurrent or metastatic ESCC in China. Methods: This trial enrolled treatment-naive pts with histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic ESCC. Eligible pts received SHR-1701 (30mg/kg, iv, d1, q3w) in combination with up to six cycles of albumin-bound paclitaxel (125mg/m 2 , iv, d1, d8, q3w) and cisplatin (75mg/m 2 , iv, d1, q3w). For those without progressive disease, maintenance treatment was administered with SHR-1701 monotherapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: At the data cut-off, March 1, 2024, 24 pts had received at least one dose of the study treatment and were included in both the intention-to-treat (ITT) analysis and safety analysis sets. 3 and 12 pts achieved confirmed complete and partial responses, respectively. The confirmed ORR was 62.5% and DCR was 87.5%. With a median follow-up of 20.8 months (95% CI, 15.5-NR), the median duration of response was 9.1 months (95% CI, 6.9-NR). The median PFS was 10.8 months (95% CI, 7.8-NR) and the median OS was 26.1 months (95% CI, 8.6-NR). 12-month PFS and OS rates were 41.4% (95% CI, 22.5-76) and 64.8% (95% CI, 47.8-87.9), respectively. Grade 3-4 treatment-related adverse events occurred in 11 (45.8%) pts and no treatment-related death was observed. Conclusions: The results highlighted that SHR-1701 plus chemotherapy as first-line therapy maintained long-term, durable survival benefit in pts with advanced ESCC. Clinical trial information: ChiCTR2000039909.

NF-κB oscillation profiles decode response to anti-EGFR monoclonal antibodies.

A direct connection between an inflammatory environment and cancer has been extensively proven over the years. We previously reported that the presence of interleukin 1 (IL-1) is responsible for the lack of response to monoclonal antibody targeting EGFR in colorectal cancer (CRC). Considering the driver role of NF-κB in controlling the expression of IL-1, herein, we investigate the dynamics of the oscillatory profile of the NF-κB response to monoclonal antibody, on the background of an inflammatory environment. NF-kB is a typical transcription factor that displays intrinsic oscillatory behavior, whose biological relevance in term for example of decoding response to monoclonal antibodies, remains unclear. Using live cell luciferase techniques, we recorded NF-κB activity over time in response to cetuximab (CTX) alone or in combination with IL-1 cytokines. Our results revealed an additive effect of these two agents on NF-κB activation, which was specific to CTX responsive cells. In contrast, CTX resistant cells did not display a significant change in the NF-κB profile under the IL-1 plus CTX combination. These results suggest an immediate interactive crosstalk between IL-1 and EGFR in the activation of NF-κB signaling pathways, which may lay the basis for the development of drug tolerant persistent cells (DTP), leading to CTX resistance.

Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes. An observational cohort of 30 adults treated with tralokinumab for ≥ 16weeks was analyzed. Clinical and demographic data were collected, and outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and numeric rating scales (NRS) for pruritus and sleep disturbances. By week16, 60% achieved a 75% improvement inEASI (EASI75)and 31% reached a 90% improvement inEASI (EASI90), reflecting substantial clinical improvements. A ≥ 4-point reduction in pruritus NRS was observed in 63% of patients by week16, increasing to 70% by week32. Similarly, 75% achieved significant improvements in sleep disturbance NRS by week16, with sustained effects through week32. Subgroup analysis revealed superior clinical responses in patients with early-onset AD and atopic comorbidities. Lower total immunoglobulinE (IgE) levels at week16 correlated with better outcomes, suggesting total IgE as a potential biomarker. By week32, 70% of patients had a DLQI ≤ 5, indicating minimal quality-of-life impact. Additionally, 88% reached at least one therapeutic target, and 81% met composite endpoints combining clinician-assessed and patient-reported outcomes. The safety profile was consistent with clinical trials, with mild conjunctivitis and injection site reactions as the most common adverse events. These findings support tralokinumab as an effective and well-tolerated treatment, emphasizing the importance of phenotype-specific approaches in AD management.

P1066 Effectiveness and safety of vedolizumab in real-world studies in Asian patients with inflammatory bowel disease: a systematic review and meta-analysis

Abstract Background Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders with rising prevalence in Asia. Vedolizumab (VDZ) is a humanized monoclonal antibody targeting α4β7 integrin, selectively blocking gut lymphocyte trafficking. Despite numerous real-world studies on VDZ use in Asian patients with IBD over recent years, a comprehensive analysis summarizing its effectiveness and safety is still lacking. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of VDZ in Asian patients with IBD. Methods A literature search was conducted to identify real-world studies evaluating intravenous VDZ in Asian patients with IBD from inception to 20th December 2023. Meta-analyses were performed separately for CD and UC patients to pool clinical and endoscopic remission and response rates across induction (6-14 weeks), medium term (22-30 weeks), and long term (over 48 or 52 weeks) using a random-effects model in R software. The incidence of adverse events (AE), serious AE (SAE), and serious infection were assessed for safety. Results Twenty-nine studies (15 CD and 25 UC) with 2,395 patients (827 CD, 1,568 UC) were analysed (Figure 1). In the induction phase, clinical response and remission were achieved in 57.48% and 61.15% of CD patients, and 64.72% and 40.07% of UC patients. In the medium term, clinical response and remission were 64.32% and 60.72% for CD, and 64.87% and 43.51% for UC. In the long term, the clinical response and clinical remission rate were 44.55% and 45.83% in CD patients, 61.35% and 56.14% in UC patients. Moreover, corticosteroid-free clinical remission was achieved by 36.58% of that in CD and 49.03% of that in UC for the long-term observation. Endoscopic response was achieved by 41.37% of CD patients and 48.57% of UC patients during induction phase. Endoscopic remission rates for CD were 11.11%, 18.41%, and 36.42%, and for UC 43.19%, 54.27%, and 66.72% in induction, medium, and long term, respectively. The pooled complete endoscopic remission rates for UC were 27.98% (induction), 47.87% (medium term), and 50.61% (long term) (Table 1). AEs occurred in 6.67% to 61.54% of CD patients and 29.69% to 75.38% of UC patients. SAEs and serious infection rates were 0.00% to 1.56% and 0.00% to 2.70% in UC patients, and 0.00% to 0.75% for serious infections in CD, with no SAEs reported in CD studies. Conclusion VDZ demonstrated effective clinical outcomes with a favourable safety profile in Asian patients with IBD.

P1100 Effectiveness of Risankizumab in Crohn’s Disease, our real-world experience: Clinical, Biochemical and Ultrasonographic responses. A single centre, observational, retrospective study

Abstract Background Risankizumab (RZB) is the first monoclonal antibody targeting IL-23 (p19 subunit) approved for moderate-to-severe Crohn’s disease (CD) patients. Clinical remission at week 12 has been reported 42-45% in the induction trials (ADVANCE, MOTIVATE), and up to 52% by week 52 at the maintenance trial (FORTIFY). Real world evidence is necessary to confirm these data. Methods We conducted an observational, retrospective, unicentric study including all adult patients with active CD who have initiated treatment with RZB. Primary endpoint is clinical remission defined as Harvey-Bradshaw Index (HBI) ≤4 for CD, both at week 12 and at the end of follow up. Secondary endpoints are: Steroid-free clinical remission, biochemical remission (defined as fecal calprotectin [FC] <250μg/g, or c reactive protein [CRP] <5mg/L), ultrasound response (defined using Ilvemark JFKF, et al 2021 Consensus Statement), and adverse events. Data are represented with median (range), and percentage. Wilcoxon, Student t-test (paired), and McNemar tests were used as appropriate. Results 34 patients were included. Full demographic description can be found in Table 1. End of follow up for HBI was on day 132.5 (93, 210). Clinical remission both at week 12 and at the end of follow up was 58.82%, steroid-free clinical remission both at week 12 and at the end of follow up was 52.94%. HBI decreased significantly from 5 (3, 9) at baseline, to 4 (2, 6) at week 12 (p=0.0471), and down to 3 (2, 6) at the end of follow up (p=0.0203). Fecal calprotectin decreased from baseline 2098.5 (490, 3003.8), to 1357.8 (805, 3077.7) at week 12 (p=0.2386), and to 1300.5 (515, 2940.7) by the end (p=0.1056). No statistically significant differences were found in the FC remission rate, nor in the CRP values and its remission rate. Transmural response assessed with ultrasound was 40% (2/5) at week 12, and 50% (4/8) at the end of follow up; transmural remission was 20% (1/5) at week 12, and 25% (2/8) at the end. There were not found differences in the intestinal ultrasound activity scores for CD. RZB was stopped in 9 (26.47%) patients, due to: primary failure 5 (2 of them required intestinal resection), secondary failure 1, and adverse events 3. Adverse events occurred in 7 (20.59%) patients: 2 arthralgias, 1 mild-moderate infusion reaction, 1 worsening of atopic dermatitis, 1 renal function impairment, 1 mild urinary tract infection, and 1 device failure. Conclusion Real world RZB effectiveness seems comparable to the efficacy reported in clinical trials. References -D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015-2030. doi:10.1016/S0140-6736(22)00467-6. -Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031-2046. doi:10.1016/S0140-6736(22)00466-4. -Ilvemark JFKF, Hansen T, Goodsall TM, et al. Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement. J Crohns Colitis. 2022;16(4):554-580. doi:10.1093/ecco-jcc/jjab173. -Barreiro-de Acosta M, Nieto García L, Poncela M, et al. OP043 Real-world short-term effectiveness of Risankizumab in refractory Crohn’s disease: RISANCROHN study from the ENEIDA registry. UEG Week 2024 Oral Presentations. United European Gastroenterol J. 2024;12(Suppl 8): 2050-6406. doi.org/10.1002/ueg2.12614.

DOP014 Efficacy and safety up to 3 years of risankizumab maintenance treatment in patients with moderately to severely active ulcerative colitis: interim results from phase 3 COMMAND open-label extension study

Abstract Background Risankizumab (RZB), a high-affinity humanised IgG1 monoclonal antibody targeting interleukin-23 p19, has shown sustained efficacy and an acceptable safety profile for patients (pts) with ulcerative colitis (UC).1 This interim analysis reports efficacy data at week (wk) 0 and wk 96, as well as safety data of the COMMAND (NCT03398135) open-label extension (OLE). Methods The COMMAND OLE enrolled pts who completed 52-wks maintenance dosing in the COMMAND substudies or entered directly from the induction study.1 All pts received RZB180 subcutaneous (SC) starting at OLE wk 0, except pts who had prior rescue therapy (single RZB 1200 mg intravenous [IV] dose then RZB360 Q8w) who continued RZB360 in the OLE. The OLE was not designed to compare RZB180 and RZB360 groups. The data cut-off date for this interim analysis was as of June 30, 2024. Efficacy endpoints assessed were clinical remission (CR) per AMS, clinical response per AMS, endoscopic improvement, endoscopic remission, and corticosteroid-free CR per Partial AMS up to wk 96. Data are reported as observed prior to RZB rescue therapy during OLE. The safety analysis also includes pts who directly entered the OLE from induction; presented as events/100 pt years (E/100 PY). Results Of the pts who entered the OLE (RZB180, N = 701; RZB360, N = 302), approximately 40% of pts had the opportunity to reach OLE wk 96 as of the cut-off date. At OLE wk 0 and 96, a similar proportion of patients in the RZB180 group achieved clinical and endoscopic outcomes (Figure 1A). In the RZB360 group, the percent of pts achieving clinical and endoscopic endpoints increased from OLE wk 0 through OLE wk 96 (Figure 1B). Similar rates of serious AEs, severe AEs, and AEs leading to discontinuation of study drug were reported in the RZB180 group and the RZB360 group with no new safety risks identified (Table 1). Conclusion In this interim analysis of the OLE, a sustained benefit was observed with long-term RZB treatment up to 96 wks. The long-term safety profile for RZB remains consistent and supports the long-term use.

Eosinophilic esophagitis in the "atopic march": dupilumab as an "umbrella" strategy for multiple coexisting atopic diseases.

Dupilumab is a monoclonal antibody targeting interleukin-4 and interleukin-13, approved for the treatment of multiple T2 diseases and more recently for Eosinophilic Esophagitis (EoE). EoE is a chronic T2 inflammatory disease, believed to be a member of the "atopic march", due to multiple similarities with other atopic diseases, ranging from epidemiology to genetics and pathophysiology. Although often co-existing in the same patient, these diseases are still treated as separated entities by different specialists, resulting in polypharmacy and chronic use of steroids. Thus, a shared-decision approach by a multidisciplinary team composed of different specialists might improve clinical management and outcomes. Yet, prospective data on the effectiveness of dupilumab as a single agent for multiple T2 inflammatory diseases are lacking, since only few case reports and small studies have been published so far reporting outcomes in patients affected by multiple T2 diseases. The purpose of this review is to illustrate the rationale and clinical evidence supporting the possibility of using dupilumab as a single therapeutic agent in those patients affected by multiple T2 diseases in addition to EoE.

Claudin 18.2 Expression in 1,404 Digestive Tract Adenocarcinomas including 1,175 Colorectal Carcinomas: Distinct Colorectal Carcinoma Subtypes are Claudin 18.2 Positive.

Claudin 18.2 (CLDN18.2) immunohistochemical expression can be used to select patients with gastric/gastroesophageal junction adenocarcinomas for zolbetuximab (IMAB362) therapy, a monoclonal antibody targeting CLDN18.2. The aim of this study was to correlate immunohistochemical expression of CLDN18.2 with clinicopathologic and molecular features in a large series of digestive tract cancers. Immunohistochemistry (IHC) for CLDN18.2 was performed on tissue microarrays from 1404 adenocarcinomas including 155 gastric/gastroesophageal, 74 pancreatic ductal, 1175 colorectal (576 in initial test cohort; 599 in subsequent validation cohort), and correlated with HER2 and mismatch repair (MMR) status. Cases were scored as CLDN18.2 positive or negative, with positivity defined as moderate to strong membranous staining in >75% of tumor cells. CLDN18.2 expression was correlated with clinicopathologic and molecular features for all colorectal adenocarcinomas. CLDN18.2 was positive in 39% (61/155) of gastric/gastroesophageal adenocarcinomas, 38% (28/74) of pancreatic ductal adenocarcinomas, and 3.4% (40/1175) of colorectal adenocarcinomas (p<0.001). For gastric/gastroesophageal and pancreatic ductal adenocarcinoma, there was no correlation between CLDN18.2 expression and either HER2 or MMR status. In contrast, CLDN18.2-positive colorectal adenocarcinomas had distinct clinicopathologic and molecular features. CLDN18.2-positive colorectal adenocarcinomas were more frequently proximally located and were more often MMR deficient and BRAF V600E positive (all with p<0.05). Quantitative pathologic analysis using the digital pathology biomarker QuantCRC demonstrated marked differences in histologic features between CLDN18.2-positive and negative colorectal adenocarcinomas, with CLDN18.2-positive tumors having increased tumor:stroma ratio and %mucin but decreased %immature stroma in both the test and validation cohorts (all with p<0.05). In conclusion, CLDN18.2-positive colorectal adenocarcinomas are frequently MMR deficient, BRAF V600E mutated, and demonstrate distinct histologic features. Future studies addressing the efficacy of zolbetuximab therapy in this subset of colorectal cancers are needed.

A Randomized, Double-Blind, Comparison of Denosumab versus Zoledronic Acid on Prolonging Bone Metastasis-Free Survival in Men with Hormone-Refractory Prostate Cancer

Bone metastases represent a critical factor contributing to illness and mortality among men diagnosed with prostate cancer. This study evaluates the therapeutic effectiveness of denosumab, a fully human monoclonal antibody targeting RANKL, in comparison to zoledronic acid for reducing the occurrence of such metastases or mortality in these patients. The investigation utilized a Cox proportional hazards model to assess bone-metastasis-free survival, factoring in variables such as chemotherapy use. Kaplan-Meier survival curves and hazard ratios (HRs) were employed to evaluate treatment differences. Results indicated that the antibody extended survival by a median of 29.97 months over its comparator. Moreover, it postponed the initial onset of metastases and improved survival outcomes. It outperformed the alternative treatment in minimizing skeletal complications and holds potential as an innovative option for men in this condition.

Incidence of Acute Kidney Injury in Relapsed and Refractory Multiple Myeloma treated with Teclistamab versus CAR T-cells.

Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B-cell maturation antigen (BCMA), and chimeric antigen receptor T-cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy. This was a retrospective study involving 64 patients with relapsed/refractory MM treated with either teclistamab or CAR-T therapy. All patients had previously received at least four lines of chemotherapy before being treated with either teclistamab or CAR-T. The primary outcome was the incidence of AKI, and secondary outcomes included AKI severity, kidney recovery rates, and mortality. Kaplan-Meier estimates for AKI-free survival were calculated, and hazard ratios (HRs) for AKI risk were determined using Cox proportional hazards models. Sixty-four patients met inclusion criteria for this study (30 received CAR-T and 34 received teclistamab therapy). Among these patients, 14 AKI events occurred in total (22%), with 10 events (29%) in the teclistamab group and 4 events (13%) in the CAR-T group. AKI-free survival estimates at 180 days after treatment initiation were 68% (95% confidence interval [CI]: 53%-87%) for teclistamab patients and 90% (95% CI: 79%-100%) for CAR-T patients. While patients receiving teclistamab were found to have an increased risk of an AKI event compared to those receiving CAR-T therapy, the results were not statistically significant (HR [95% CI]: 3.38 [0.93-12.31], P=0.065). This study suggests that patients treated with teclistamab may experience a higher incidence of AKI compared to those receiving CAR-T therapy. However, further research is required to determine whether this increased risk is attributable to disease progression or teclistamab itself. These results highlight the need for close kidney function monitoring in patients receiving teclistamab.

Unveiling the safety profile of lecanemab: A comprehensive analysis of adverse events using FDA adverse event reporting system data.

Lecanemab, a novel monoclonal antibody targeting amyloid-β, has shown promise in treating Alzheimer's disease. Comprehensive post-marketing safety data analysis is crucial to understand its real-world risk profile. This study aimed to evaluate the safety profile of lecanemab using data from the FDA Adverse Event Reporting System (FAERS), with a focus on nervous system disorders and amyloid-related imaging abnormalities. We conducted a disproportionality analysis using the FAERS database to evaluate the safety signals associated with lecanemab. Reporting odds ratio (ROR), proportional reporting ratio, empirical Bayesian geometric mean, and information component were calculated at both system organ class (SOC) and preferred term (PT) levels. Additionally, we performed a time-to-onset analysis using Weibull shape parameter estimation. Analysis at the SOC level revealed significant signals for nervous system disorders (ROR: 7.32, 95% CI: 6.69-8.00). At the PT level, strong signals were observed for amyloid-related imaging abnormalities, particularly those associated with microhemorrhages and oedema (ROR: 4122.81 and 3922.78, respectively). Headache was the most frequently reported adverse event (200 cases), followed by chills (107 cases) and fatigue (97 cases). Time-to-onset analysis showed a median time of 33 days (range: 1-1283) for all adverse events, with neurological events occurring slightly later (median: 42 days, range: 1-1260). Our findings highlight a distinct safety profile for lecanemab, with a predominant impact on the nervous system and a notable association with imaging abnormalities. These results underscore the importance of vigilant monitoring and further research to optimize the risk-benefit profile of lecanemab in clinical practice.

HER2-Positive Breast Cancer Treatment and Resistance.

HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents. Efforts to develop new treatment regimens to treat/overcome resistance is futile without a primary understanding of the mechanistic underpinnings of resistance. Resistance could be attributed to mechanisms that are either specific to the tumor epithelial cells or those that emerge through changes in the tumor microenvironment. Reactivation of the HER receptor layer due to incomplete blockade of the HER receptor layer or due to alterations in the HER receptors is one of the major mechanisms. In other instances, resistance may occur due to deregulations in key downstream signaling such as the PI3K/AKT or RAS/MEK/ERK pathways or due to the emergence of compensatory pathways such as ER, other RTKs, or metabolic pathways. Potent new targeted agents and approaches to target key actionable drivers of resistance have already been identified, many of which are in early clinical development or under preclinical evaluation. Ongoing and future translational research will continue to uncover additional therapeutic vulnerabilities, as well as new targeted agents and approaches to treat and/or overcome anti-HER2 treatment resistance.

The Clinical Utility of the Ocrelizumab for the Patients with Multiple Sclerorsis

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, primarily affecting young adults, and is characterized by demyelination and neurodegeneration. Although several disease-modifying therapies (DMTs) are available in Korea, patients who experience inadequate responses or disease progression continue to require more effective and safer therapeutic options. Ocrelizumab, a humanized monoclonal antibody targeting CD20 of B cells, has shown high efficacy in both relapsing forms of multiple sclerosis and primary progressive multiple sclerosis patients. It was approved by the Food and Drug Administration in 2017 and approved by Ministry of Food and Drug Safety Korea in 2024. Clinical trials such as the OPERA and ORATORIO studies demonstrated that ocrelizumab significantly reduced relapse rates, disability progression, and magnetic resonance imaging lesions compared to interferon beta 1a or placebo. Real-world data further supports its clinical value, showing similar or superior efficacy to other high-efficacy DMTs. Long-term safety profile of ocrelizumab remains favorable, with manageable risks such as infections, particularly lower respiratory tract and urinary tract infections. This review discusses the clinical value of ocrelizumab in the treatment of multiple sclerosis, its potential as a tolerable high efficacy treatment option for patients in need of more effective therapies. Based on the clinical evidence, ocrelizumab offers a promising therapeutic opportunity for Korean MS patients, especially those with high disease activity, and is expected to become an essential part of MS treatment strategies worldwide.

Therapeutic potential of a systemically applied humanized monoclonal antibody targeting Toll‑like receptor 2 in atopic‑dermatitis‑like skin lesions in a mouse model.

Atopic dermatitis (AD) is a prevalent, persistent inflammatory skin disorder distinguished by pruritic and irritated skin. Toll-like receptors (TLRs) are specialized receptors that recognize specific patterns associated with pathogens and tissue damage, triggering an innate immune response that protects the host from invading pathogens. Previously, it was demonstrated that intradermal injection of the humanized anti-TLR2 monoclonal antibody (Ab) Tomaralimab effectively relieved AD-like skin inflammation in BALB/c mouse models exposed to house dust mite extracts. However, it remains unclear whether allergenic hapten-induced AD can be effectively treated with systemically administered TLR2-targeting Abs. In the present study, it was observed that administrating Tomaralimab through intravenous injection alleviated AD-like skin lesions in BALB/c mice challenged with topical application of 2,4-dinitrochlorobenzene by reducing the infiltration of inflammatory cells into skin lesions and preventing the creation of various inflammatory cytokines, including thymic stromal lymphopoietin, interleukin (IL)-4, IL-13, IL-17 and IL-31, which are associated with the pathogenesis of AD. These findings support the feasibility of using a humanized anti-TLR2 monoclonal Ab as systemic therapy for AD.

Advancements in Early Alzheimer’s Treatment: Narrative Review about Lecanemab (Leqembi ®)

Alzheimer's disease represents one of the most significant challenges in the field of neurology, affecting millions of individuals worldwide. In pursuing efficacious treatments, lecanemab has emerged as a promising therapeutic option. This pioneering monoclonal antibody targets and reduces amyloid-beta plaques in the brain, a defining feature of Alzheimer's disease. By addressing one of the fundamental causes of the disease, lecanemab represents a novel approach to slowing its progression. On 14th November 2024, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting marketing authorisation for Leqembi® (whose active substance is lecanemab). This recommendation is specifically directed towards patients with early-onset Alzheimer's disease who are non-carriers or heterozygotes for the apolipoprotein E ε4 (ApoE ε4) allele, thereby underscoring the drug's efficacy tailored to specific genetic profiles (Committee for Medicinal Products for Human Use, 2024). The CHMP's approval is a testament to the extensive research and clinical trials that have demonstrated the efficacy and safety of Leqembi® (Lecanemab). This narrative review aims to provide a comprehensive examination of these aspects and offer a detailed understanding of the potential impact of this treatment on the management of early Alzheimer's disease.

Efficacy and safety of camrelizumab for the treatment of cervical cancer: a systematic review and meta-analysis.

Cervical cancer (CC) is a prevalent malignancy in women and ranks fourth in global cancer-related mortality. The prognosis for women with metastatic or recurring cervical cancer is unfavorable. Camrelizumab is a humanized high-affinity IgG4-kappa monoclonal antibody targeting programmed cell death 1 (PD-1), which has been progressively documented as a therapy for advanced cervical cancer with good result metrics. Nonetheless, a comprehensive investigation of Camrelizumab's efficacy in treating cervical cancer has yet to be conducted. We conducted a search across PubMed, Ovid Medline, Embase, Web of Science, Cochrane Library, Scopus, ProQuest, CNKI, Wan Fang, VIP database, and CBMdisc, restricting the establishment date of the databases to October 2024. The ROBINS-I Scale was utilized to evaluate the methodological quality of the included studies. Furthermore, information about CR, PR, SD, PD, ORR, DCR, median OS, median PFS, adverse events (AEs), and other relevant data was obtained. A meta-analysis was performed utilizing a random-effects model and effect size for illness. This meta-analysis included six trials, including 238 people with CC. The aggregated outcomes for patients were as follows: CR (0.097, 95% CI: 0.032-0.186), PR (0.465, 95% CI: 0.291-0.638), SD (0.264, 95% CI: 0.124-0.403), PD (0.174, 95% CI: 0.051-0.296), ORR (0.577, 95% CI: 0.354-0.799), DCR (0.784, 95% CI: 0.652-0.916), AEs (all grades: 0.836, 95% CI: 0.629-1.000, ≥grade III: 0.472, 95% CI: 0.111-0.834). The predominant treatment-related adverse events included anemia (≤grade II: 0.295, 95% CI: 0.187-0.402; ≥grade III: 0.124, 95% CI: 0.018-0.230), elevated aspartate aminotransferase (≤grade II: 0.196, 95% CI: 0.013-0.380; ≥grade III: 0.030, 95% CI: 0.007-0.053), neutropenia (≤grade II: 0.206, 95% CI: 0.150-0.261; ≥grade III: 0.114, 95% CI: 0.066-0.162), thrombocytopenia (≤grade II: 0.295, 95% CI: 0.187-0.402), and fatigue (≤grade II: 0.174, 95% CI: 0.046-0.303). This meta-analysis demonstrates that camrelizumab is efficacious and well-tolerated in patients with cervical cancer. https://www.crd.york.ac.uk/prospero/, identifier CRD42024527065.