Safety Management Research Articles

Comparison between spinal fusion vs. nonoperative treatment for lumbar degenerative pathology: a systematic review and meta-analysis.

Lumbar fusion is widely used to treat chronic lumbar degenerative pathology; however, its effectiveness and safety compared with nonoperative management remain controversial. This systematic review and meta-analysis aimed to evaluate and compare the effectiveness and safety of spinal fusion and conservative management in treating lumbar degenerative pathology. A systematic review and meta-analysis were conducted following the PRISMA guidelines. The PubMed, Scopus, Cochrane Central, Web of Science, and Embase databases were searched in October 2024. Eligible studies included randomized controlled trials (RCTs) and observational studies reporting pain reduction and functional disability outcomes. The primary outcomes were changes in the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) scores for back and leg pain. Data were analyzed using a random-effects model in RevMan 5.4.1, with subgroup and sensitivity analyses performed to address heterogeneity. Fourteen studies comprising 13 RCTs and one cohort study, involving 2,399 participants, were included. Spinal fusion showed significant improvements in ODI scores compared to conservative treatment (MD = -6.3; 95% CI [-12.02, -0.57]; p = 0.03), indicating reduced disability. VAS back pain scores also favored spinal fusion (MD = -3.02; 95% CI [-5, 1.04]; p = 0.003), with long-term outcomes showing consistent benefits (MD = -2.26; 95% CI [-3.16, 1.37]; p < 0.00001). However, spinal fusion did not significantly reduce leg pain compared to non-operative options (MD = -2.27; 95% CI [-8.37, 3.83]; p = 0.47). Spinal fusion offers statistically significant benefits in reducing disability and back pain compared with conservative treatments for lumbar degenerative pathology. However, it does not confer substantial advantages to leg pain and carries a high surgical risk. These findings emphasize the importance of individualized treatment selection based on patient characteristics and clinical indications.

The Efficacy and Safety of a Personalized Protocol Designed to Balance Hemoglobin Levels in Hemodialysis Patients as Led by Nephrology Clinical Nurse Specialists: An Intervention Study.

Background: The ongoing clinical challenge of managing hemoglobin levels in chronic dialysis patients is exacerbated by the gap between growing patient needs and the limited availability of nephrologists. Clinical nurse specialists (CNSs) have been contributing to the successes of modern healthcare systems across Europe, but there is a limited understanding of specific mechanisms by which CNSs can support and improve patient outcomes in renal diseases. Objectives: Responding to previous calls, this intervention study evaluated the role of nephrology CNSs in dialysis patient care. Methods: This intervention study employed erythropoiesis-stimulating agents (ESAs) to investigate whether a personalized, tailored protocol led by nephrology CNSs could improve the hemoglobin balance compared to the conventional standard of care led by nephrologists. Thirty-nine patients who met the inclusion criteria with a preset hemoglobin value between 10.5-12 g/dL completed the study. Results: There were no significant differences in hemoglobin levels between patients managed by nephrologists and those overseen by CNSs. Hemoglobin variability remained unchanged after protocol implementation, while key dialysis quality indicators (e.g., iron saturation, urea reduction) remained within safety limits. Notably, ESA-related medical adjustments were significantly reduced, requiring half as many modifications over 12 study points. Conclusions: A CNS-led personalized protocol effectively maintained dialysis patient parameters within established safety thresholds. These findings reinforce the critical role of CNSs in enhancing the efficiency, effectiveness, and safety of hemoglobin management in this high-risk population. Policy implications are discussed.

Effectiveness and safety of multimodal analgesic management based on the ERAS concept in the perioperative period of TACE for patients with Intermediate and advanced hepatocellular carcinoma.

12085 Background: To evaluate the effectiveness and safety of multimodal analgesic management based on the enhanced recovery after surgery (ERAS) concept in the perioperative period of transarterial chemoembolization (TACE) for patients with advanced hepatocellular carcinoma. Methods: A retrospective analysis was conducted on 90 patients who underwent TACE at the First Affiliated Hospital of Sun Yat-sen University from January 2022 to October 2023. Patients were divided into two groups: Group A received a multimodal analgesic regimen based on the ERAS concept, which included preoperative administration of 6 mg hydromorphone hydrochloride and 50 mg flurbiprofen axetil, diluted in normal saline to a total of 100 ml and infused via a patient-controlled intravenous analgesia (PCIA) pump. Group B received conventional perioperative management combined with traditional analgesic methods, using intravenous flurbiprofen axetil 50 mg or intramuscular tramadol 100 mg for postoperative pain. Pain levels were recorded using the Numeric Rating Scale (NRS) at various time points: intraoperatively, immediately postoperatively, and at 1, 6, 12, and 24 hours post-surgery, along with the incidence of adverse reactions within 24 hours. Inflammatory indicators were compared before and after TACE, and patient satisfaction and cost-effectiveness analyses were conducted. Results: The NRS scores for Group A at the five time points were 3.0 (3.0–2.0), 3.0 (4.0–2.0), 4.0 (5.0–3.0), 3.0 (3.5–2.0), and 1.0 (1.0–0.5), respectively. For Group B, the scores were 4.0 (5.0–3.0), 4.0 (5.0–3.0), 5.0 (6.0–3.5), 3.0 (4.0–2.0), and 1.0 (2.0–1.0) , respectively. Except for the NRS score at 12 hours post-surgery, all other time points showed statistically significant differences. There was no statistically significant difference in the levels of PCT and IL-6 before and after surgery between the two groups, but a trend of lower postoperative PCT and IL-6 levels in Group A compared to Group B was observed. The incidence of various adverse reactions 24 hours post-surgery did not differ significantly between the two groups (P &gt; 0.05). Patient satisfaction with analgesia at 48 hours post-surgery was significantly higher in Group A than in Group B, with a statistically significant difference (P = 0.001). Group A demonstrated better economic benefits. Conclusions: The results of this study indicate that multimodal analgesic management based on the ERAS concept has better analgesic effects during the perioperative period of TACE treatment, with comparable safety and improved economic benefits. This provides strong support for the clinical application of multimodal analgesic management based on the ERAS concept in TACE for liver cancer.

A review on the use of top-view surveillance videos for pedestrian detection, tracking and behavior recognition across public spaces.

A review on the use of top-view surveillance videos for pedestrian detection, tracking and behavior recognition across public spaces.

Mycotoxin management in Sub-Saharan Africa: A comprehensive systematic review of policies and strategies in Malawi.

Food safety challenges, such as mycotoxin contamination, pose severe threats to public health, agricultural productivity, and economic development across Sub-Saharan African countries and beyond. This study investigated whether government policies related to food safety adequately address these concerns, using Malawi as a case study. We systematically reviewed 29 government-authored policy documents related to food safety. These documents were categorized into six sectors: Agriculture, Environment, Nutrition, Health, Trade and Industry, and Education. Our analysis revealed critical gaps in addressing mycotoxin concerns in these policies, with only 4 of the 29 policy documents (14 %) addressing food safety and mycotoxin management. In contrast, 13 policy documents (45 %) did not address these issues at all, while 12 policy documents (41 %) focused solely on food safety management without addressing mycotoxin contamination. Notably, Malawi's long-term development blueprint, Malawi 2063 , does not include mycotoxin management, underscoring a critical policy gap and broader systemic challenges in integrating food safety and mycotoxin control into national frameworks. Furthermore, Malawi lacks a dedicated sector responsible for food safety and a comprehensive national food safety policy to coordinate efforts in mycotoxin control. While this study centers on Malawi, the findings resonate globally, particularly in Sub-Saharan Africa and other countries with similar agricultural and economic contexts. Addressing these systemic policy gaps is vital for developing integrated food safety frameworks that combat mycotoxin contamination, strengthen sustainable food systems, enhance public health, and foster economic resilience. These findings also provide a replicable model for policy analysis, contributing to international discourse by emphasizing the importance of aligning food safety governance with global development priorities, such as the Sustainable Development Goals.

RC48-ADC combined with radiotherapy and immunotherapy as salvage therapy for advanced solid tumors with HER2 expression: A multicenter, phase II trial.

3032 Background: Antibody-drug conjugates (ADC) have demonstrated efficacy in treating tumors with HER2 over expression. However, the clinical benefits of ADCs are limited in tumors with lower HER2 expression. The combination of ADCs, radiotherapy, and immunotherapy has shown promising feasibility with HER2-expressing tumors across various cancer types. This approach can enhance spatial and physicochemical synergistic effects, resulting in a more diverse and increased release of tumor antigens. Subsequently, PD-1 inhibitors activate effector T cells, generating a robust immune response that targets and eliminates tumor cells. A single-arm, multicenter phase II trial was initiated to evaluate the clinical efficacy of RC48-ADC combined with radiotherapy and immunotherapy, in HER2-expressing advanced solid tumors. The findings from this trial may establish a new salvage treatment strategy for tumors with low HER2 expression. Methods: This study enrolled patients with advanced, HER2-expressing (IHC 1+, 2+, or 3+) solid tumors that had progressed following standard therapies or due to intolerance. Participants received RC48 (disitamab vedotin, 2.0 mg/kg on day 1), followed by radiotherapy every other day (2-3 fractions of 5-8 Gy), GM-CSF 200 μg on days 3-7), sequential IL-2 (2 million IU on days 8-12), and a PD-1 inhibitor administered within one week after completing radiotherapy. This regimen was repeated every three weeks. The primary endpoint was the objective response rate (ORR). Results: As of the cutoff date (December 31, 2024), 52 patients were enrolled, including 10 with gynecological cancers, 10 with pancreatic cancer, and 32 with various other tumor types (including breast, gastric and colorectal cancers). All participants had evaluable data. According to RECIST 1.1, the overall ORR was 36.5%, with two patients achieving a complete response (CR) that lasted nearly two years, maintaining minimal residual disease negative status. The ORRs for patients with HER2 expression of 1+, 2+, and 3+ were 29.0%, 43.4%, and 60.0%, respectively. The median progression-free survival (PFS) for all patients was 5.9 months (95% CI: 4.1–9.7 months). The median overall survival (OS) for all patients was 14.3 months (95% CI: 8.6–15.7 months).Treatment-related adverse events were predominantly mild (grade 2 or lower), including fatigue, hair loss, nausea, fever, and rash. Only three patients (5.8%) experienced grade 3 adverse events. Conclusions: The results indicate promising efficacy and manageable safety, with a favorable short-term tumor response rate. This suggests that the combination of RC48-ADC, radiotherapy, and immunotherapy could serve as an effective salvage therapy option for patients with HER2-expressing advanced solid tumors. The combination therapy appears to enhance the synergistic effects of radiotherapy and immunotherapy. Clinical trial information: NCT0511550 .

Immune checkpoint inhibitors for ovarian cancer: A retrospective analysis of efficacy and tolerability.

e17574 Background: Ovarian cancer (OC) is the leading cause of gynecological cancer-related deaths. Despite standard treatments, most advanced cases recur within three years, highlighting the need for novel therapies. Although immune checkpoint inhibitors (ICIs) have shown limited benefits in OC so far, combining them with other treatments may improve outcomes. This study assesses the safety, tolerability, and antitumor efficacy of ICIs in OC patients in a real-world setting. Methods: Patients who had received at least one ICI treatment at Zhongnan Hospital of Wuhan University between January 1, 2018, and April 3, 2024, were enrolled. The primary endpoint was the confirmed objective response rate (ORR) according to RECIST version 1.1 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs). Results: A total of thirty-nine ovarian cancer patients (median age, 56 years) treated with ICIs were included in the analysis. Following a median follow-up period of 19.55 months, the ORR was determined to be 20.5%, comprising 2 complete responses and 6 partial responses. Additionally, 12 patients (30.8%) achieved stable disease. The median PFS was 6.3 months (95% CI, 3.8-8.8), while the median OS was 9.7 months (95% CI, 4.7-14.7). Earlier use of ICIs, platinum sensitiveness were associated with improved PFS. Treatment-related adverse events of grade 3 or higher were observed in 6 patients (15.38%). Conclusions: The study findings suggest that ICIs exhibit potential antitumor activity with manageable safety and toxicity profiles in patients with ovarian cancer, indicating the need for further investigation.

Updated results from a multicenter, single-arm phase II study of surufatinib plus sintilimab and IBI310 in patients with high-grade advanced-neuroendocrine neoplasm (HG-NEN).

e16342 Background: HG-NEN are highly aggressive and associated with poor prognosis. Surufatinib (SUR), a selective inhibitor of VEGFRs, FGFR1, and CSF-1R, has emerged as a promising therapeutic agent in combination with immune checkpoint inhibitors (ICIs) based on preclinical and clinical studies. Ipilimumab (anti-CTLA-4 antibody) plus nivolumab (anti-PD-1 antibody) is recommended by the NCCN guidelines for extrapulmonary and non-pancreatic neuroendocrine carcinomas (NEC) that progress after chemotherapy. This study aims to evaluate the efficacy and safety of SUR plus sintilimab (SIN, an anti-PD-1 antibody) and IBI310 (IBI, an anti-CTLA-4 antibody) in patients (pts) with advanced grade-3 neuroendocrine tumors (G3 NETs) and NECs. Methods: Eligible HG-NEN pts included those who had failed, could not tolerate, were not suitable for, or refused to receive standard treatment. Pts received SUR (250mg, qd, po, q3w) combined with SIN (200mg, d1, i.v.gtt, q3w) and IBI (1mg/kg, d1, i.v.gtt, q6w). The primary endpoint was ORR. Secondary endpoints included PFS, OS, DCR and safety. ORR and DCR were based on the efficacy evaluable analysis set (EEAS) - all pts who received ≥ 1 doses of the study drug and had ≥ 1 valid post-baseline tumour assessments. Supportive analyses were conducted for the full analysis set (FAS) population. Baseline characteristics, safety, PFS, and OS were analysed in the FAS population. Results: As of Jan 06, 2025, 31 pts were enrolled, with 5 withdrawn due to drug intolerance (3 immune myocarditis, 1 immune pancreatitis, 1 thrombocytopenia) and 2 due to tumor-related SAEs. The EEAS included 24 pts, and the FAS included all 31 pts. Median age was 55 years (range: 22–71), with 67.7% male, 61.3% ECOG PS 1, and 93.5% with NEC. Median ki-67 was 80% (range: 25%-90%), with 77.4% ki-67 &gt; 55%. 90.3% pts received prior systemic therapy (51.6% 1L and 38.7% ≥2L). The median follow-up time was 16.8 months. The mPFS was 3.8 (95% Cl: 2.8-4.5) months, with an ORR of 37.5% and DCR of 75%. The mOS was not reached. The 12-month OS rates were 63.1% and 76.6% in the FAS and EEAS population. In 15 pts who had received no more than one previous systemic regimens, the mPFS was 4.4 (95%Cl: 3.3-16.2) months, with an ORR of 46.7% and DCR of 80.0%. The 12-month OS rates were 68.4% and 82.5% in the FAS and EEAS population. 48.4% pts experienced rade ≥3 treatment-related adverse events (TRAEs). Conclusions: Surufatinib combined with sintilimab and IBI310 demonstrated promising efficacy and manageable safety in HG-NEN, with greater benefit observed in earlier treatment lines. This regimen may offer a new therapeutic option for patients with HG-NEN. Clinical trial information: NCT05165407 .

First results of an open-label, single arm phase II trial investigating the efficacy and safety of trifluridine/tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma.

4121 Background: Cholangiocarcinoma (CCA) is a rare and aggressive malignancy with poor prognosis. Although firstline therapy with gemcitabine, cisplatin and durvalumab has been established based on the TOPAZ-1 trial, treatment options for subsequnt therapies remain limited. The TRITICC study investigated the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with disease progression after firstline treatment. Methods: TRITICC was a phase IIA, interventional, prospective, open-label, non-randomized, exploratory, multicenter, single-arm trial. Adult patients with histologically confirmed, locally advanced or metastatic biliary tract cancer received FTD/TPI (25 mg/m² BSA, BID, orally, days 1–5 of each 14-day cycle) combined with irinotecan (180 mg/m² on day 1 of each cycle). Progression free survival (PFS) was the primary endpoint. Secondary endpoints included the PFS rate at 4 months, median overall survival (OS), objective response rate (ORR), and quality of life. The trial was registered with ClinicalTrials.gov (NCT04059562) and EudraCT (2018-002936-26). Results: 28 patients were enrolled across six sites in Germany. The median PFS was 3.1 months (95% CI: 2.0–7.5), with PFS rates of 35% (95% CI: 21%–58%) at 4 months, 30% (95% CI: 17%–54%) at 6 months, and 13% (95% CI: 4.7%–37%) at 12 months. PFS and PFS rates were higher in patients with intrahepatic CCA (iCCA). The OS rates were 74% (95% CI: 59%–93%) at 6 months and 38% (95% CI: 22%–68%) at 12 months. Similar to the PFS rates the OS rates were higher in iCCA. Among 27 evaluable patients, partial responses were observed in 3 patients (11.1%, 2 iCCA, 1 eCCA), stable disease in 11 patients (40.7%, 7 iCCA, 4 eCCA). Thirteen patients (48.1%, 7 iCCA, 6 eCCA) experienced disease progression. Outcomes due to tumor location will have to be examined in higher patient numbers. The most frequently reported adverse events included neutropenia, thrombocytopenia, gastrointestinal symptoms and fatigue. The mean Global Health Status score (EORTC QLQ-C30) declined moderately from 56.2 at screening to 46.4 at the end of treatment. No severe, unmanageable or unexpected toxicities were reported. Conclusions: The combination of FTD/TPI and irinotecan demonstrated promising efficacy and manageable safety in CCA patients progressing after first-line gemcitabine-based therapy, aligning with recent findings in comparable populations (e.g., Tella et al.). Further investigations are warranted to validate these results. The NIFTY trial suggested that pegylated irinotecan may enhance efficacy compared to conventional irinotecan, a hypothesis that will be explored in the planned follow-up TRITICC-2 study. The study was funded by Servier Deutschland GmbH and Servier Affaires Médicale. Clinical trial information: NCT04059562 .

Efficacy and safety of RC48-ADC in triple-negative breast cancer subtypes: FUSCC-TNBC-umbrella trial results.

1109 Background: RC48-ADC is a novel HER2-targeting antibody-drug conjugate. This study evaluated RC48-ADC in pretreated triple-negative breast cancer (TNBC) patients with low HER2 expression, stratified by AR status. Methods: In this phase Ib/II trial, pretreated metastatic TNBC patients with low HER2 expression were enrolled: RL group (LAR subtype, n=20) and RO group (non-LAR subtype, n=20). All received RC48-ADC 2.0 mg/kg intravenously every 2 weeks. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: 40 heavily pretreated patients were enrolled (median 2 previous lines, range 1-7). In the overall population, best ORR was 35.0% (confirmed ORR: 32.5%), DCR 47.5%, median PFS 4.0 months. RL group showed better outcomes: best ORR 45.0% vs 25.0%, confirmed ORR 40.0% vs 25.0%, DCR 50.0% vs 45.0%, median PFS 4.9 vs 3.1 months. Median OS was not reached in RL group vs 16.6 months in RO group. Most common treatment-related adverse events (TRAEs) were AST increased (70% vs 40%) and ALT increased (65% vs 20%), mostly grade 1-2. Peripheral neuropathy occurred in 15% (RL) and 10% (RO) patients. Hematologic toxicities were mild. No treatment-related deaths occurred. Conclusions: RC48-ADC showed promising antitumor activity with manageable safety in pretreated TNBC patients with low HER2 expression, particularly in LAR subtype. The 35.0% ORR in heavily pretreated TNBC warrants further investigation in biomarker-selected populations. Clinical trial information: NCT03805399 . Efficacy and key safety outcomes of RC48-ADC in overall population and by subgroups. Outcomes Overall (n=40) RL Group (n=20) RO Group (n=20) Efficacy Confirmed ORR, n (%) 13 (32.5) 8 (40.0) 5 (25.0) Best ORR, n (%) 14 (35.0) 9 (45.0) 5 (25.0) DCR, n (%) 19 (47.5) 10 (50.0) 9 (45.0) Median PFS, months 4 4.9 3.1 Median OS, months NR NR 16.6 Best Response, n (%) CR 1 (2.5) 1 (5.0) 0 (0.0) PR 13 (32.5) 8 (40.0) 5 (25.0) SD 5 (12.5) 1 (5.0) 4 (20.0) PD 21 (52.5) 10 (50.0) 11 (55.0) Selected TRAEs, n (%) AST increased - Grade 1-2 22 (55.0) 14 (70.0) 8 (40.0) - Grade ≥3 0 (0.0) 0 (0.0) 0 (0.0) ALT increased - Grade 1-2 17 (42.5) 13 (65.0) 4 (20.0) - Grade ≥3 0 (0.0) 0 (0.0) 0 (0.0) Peripheral neuropathy - Grade 1-2 3 (7.5) 2 (10.0) 1 (5.0) - Grade ≥3 2 (5.0) 1 (5.0) 1 (5.0)

JSKN003, a biparatopic HER2-targeting ADC, in heavily pretreated HER2-positive breast cancer: A pooled analysis of early-phase studies.

1028 Background: JSKN003 is a biparatopic HER2-targeting antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor (TOP1i) via a tetrapeptide linker, designed to enhance serum stability and anti-tumor activity. The efficacy and safety of JSKN003 in advanced ovarian cancer and other solid tumors have been highlighted in previous reports, and this analysis provides updated insights into its performance in HER2-positive breast cancer. Methods: JSKN003-101 is a dose-escalation and -expansion study in Australia, and JSKN003-102 is a phase I/II study in China, both involving patients with advanced solid tumors. A pooled analysis was performed to assess its efficacy and safety in HER2-positive advanced breast cancer. Results: As of November 29, 2024, the median follow-up duration was 3.52 months (range: 2.99-3.71). A total of 71 patients with HER2-positive breast cancer were enrolled, with the majority receiving 6.3 mg/kg or 8.4 mg/kg doses. The median age was 54 years (range: 32-79), with 78.9% ECOG 1. All patients had stage IV disease, with 76.1% having visceral metastases. All patients had prior anti-HER2 therapy, including 87.3% with prior ADCs or TKIs, and 56.3% having ≥3 prior lines. Among 62 evaluable patients, 56 were T-DXd naïve. In these 56 patients, the overall response rate (ORR) was 67.9% (95%CI: 54-79.7), and the disease control rate (DCR) was 94.6% (95%CI: 85.1-98.9). In the RP2D subgroup (6.3mg/kg, n = 30), the ORR was 70.0% (95%CI:50.6-85.3). Of 6 patients with prior T-DXd exposure, 1 achieved a partial response (PR), 3 had stable disease (SD), and tumor shrinkage was observed in 3. Both median progression-free survival (PFS) and median overall survival (OS) were immature. Treatment-related adverse events (TRAEs) ≥Grade 3 occurred in 11.3% of patients, and serious adverse events (SAEs) in 9.9%, with 2 drug-related. No TRAEs led to death or treatment discontinuation. The most common TRAEs (≥20%) included nausea, elevated liver enzymes, vomiting, decreased appetite, fatigue, diarrhea, and anemia. No≥Grade 3 neutropenia was observed. Grade ≥3 anemia and decreased platelet count were each reported in 1 patient (1.4%), both being Grade 3. Interstitial lung disease (ILD) occurred in three patients (4.2%), all Grade 1-2, with no Grade ≥3 events. Conclusions: JSKN003 demonstrated promising efficacy and manageable safety in heavily pretreated HER2-positive breast cancer, including T-DXd-experienced patients. The biparatopic HER2 antibody design likely enhanced its binding efficiency and contributed to the observed clinical benefit. These findings support the planned Phase 3 trial to further evaluate its therapeutic potential. Clinical trial information: NCT05494918 ; NCT05744427 .

Pembrolizumab monotherapy for melanoma or non-small cell lung cancer in India: Results of the phase IV keynote-593 study.

e21518 Background: The PD-1 inhibitor pembrolizumab has been shown to provide a significant overall survival (OS) benefit with manageable safety in global clinical studies of advanced melanoma and non-small cell lung cancer (NSCLC); however, these trials did not include any participants from India. KEYNOTE-593 (NCT03715205) is a prospective, open-label, phase IV study designed to evaluate the safety of pembrolizumab in participants from India with advanced melanoma or NSCLC. Methods: Eligible participants had unresectable stage III or IV melanoma and ≤1 prior line of systemic therapy; stage IIIB-IV NSCLC with PD-L1 tumor proportion score (TPS) ≥1% and ≥1 prior line of systemic therapy; or stage IV NSCLC with TPS ≥50%, no EGFR or ALK alteration, and no prior systemic therapy. All participants received pembrolizumab 200 mg Q3W for ≤35 cycles. The primary end point was safety. Efficacy was not formally assessed, but response data were collected as part of routine participant management. Follow-up continued until 30 days after last dose of pembrolizumab or before start of new anticancer therapy, whichever was earlier. Results: A total of 150 participants were enrolled. Among the 118 participants with melanoma, the median age was 56.0 years, 115 (97.5%) had stage IV disease, 40 (33.9%) had mucosal melanoma, 10 (8.5%) had acral lentiginous melanoma, and 89 (75.4%) were previously untreated. Among the 32 participants with NSCLC, the median age was 64.5 years, 28 (87.5%) had stage IV disease, and 26 (81.3%) had received prior treatment (1 prior line, n = 10 [31.3%]; 2 prior lines, n = 10 [31.3%]; ≥3 lines, n = 6 [18.8%]). As of the database cutoff (Aug 21, 2024), median study follow-up was 4.2 months (range, 0.7-28.2); 106 participants (89.8%) with melanoma and 28 participants (87.5%) with NSCLC had discontinued treatment, most commonly due to progressive disease (n = 82 [69.5%] and n = 16 [50.0%], respectively). Any cause adverse events (AEs) occurred in 131 participants (87.3%); grade 3-5 AEs occurred in 38 (25.3%). Treatment-related AEs occurred in 61 participants (40.7%); grade 3-5 treatment-related AEs occurred in 11 (7.3%). Four treatment-related deaths occurred (hepatic failure, pneumonitis, ischemic stroke, and cardiac tamponade). Immune-mediated AEs occurred in 33 participants (22.0%), of which the most common (≥5%) was hypothyroidism (17.3%). Grade 3-5 immune-mediated AEs occurred in 5 participants (3.3%). The objective response rate per RECIST v1.1 by investigator review was 11.0% (95% CI, 6.0-18.1; 13 partial response) in participants with melanoma and 12.5% (95% CI, 3.5-29.0; 4 partial response) in participants with NSCLC. Conclusions: The safety profile of pembrolizumab in participants from India with advanced melanoma or NSCLC was no different from what has been reported in global studies. Antitumor activity was observed in the exploratory analysis of efficacy. Clinical trial information: NCT03715205 .

Outcomes by baseline tumor burden using the 6-and-12 score in EMERALD-1: A phase 3 study of durvalumab (D) ± bevacizumab (B) with transarterial chemoembolization (TACE) in embolization-eligible unresectable hepatocellular carcinoma (uHCC).

4083 Background: In EMERALD-1 (NCT03778957), D + B + TACE significantly improved progression-free survival (PFS) vs TACE in participants (pts) with embolization-eligible uHCC. Tumor burden is a prognostic factor in HCC. Prior analyses showed improvements in PFS with D + B + TACE vs TACE in pts who met or exceeded the up-to-7 criterion (a measure based on tumor number and size), and in those with max tumor diameters of &lt; 10 cm or ≥10 cm. The 6-and-12 score measures tumor burden based on tumor number and size. We assessed outcomes in EMERALD-1 by baseline tumor burden using the 6-and-12 score. Methods: Pts were randomized 1:1:1 to D + B + TACE, D + TACE, or TACE. Pts received D (1500 mg) or PBO for D (Q4W) + TACE. After completing the last TACE, pts received D (1120 mg) + B (15 mg/kg), D (1120 mg) + PBO for B, or PBOs for D and B (Q3W). In pts who received D + B + TACE and TACE, PFS, time to progression (TTP), and objective response rates (ORR), per BICR RECIST v1.1 in the intent-to-treat (ITT) population, and safety and number of TACE cycles in the safety analysis set (SAS; pts received ≥1 dose of study treatment [tx], regardless of randomization) are reported by baseline tumor burden using 6-and-12 scores: ≤6, &gt; 6–12, or &gt; 12. Results: Overall, 40.0%, 43.9%, and 16.2% of pts belonged to the ≤6, &gt; 6–12, and &gt; 12 groups, respectively. The number of pts who received ≥2 TACE cycles increased across the groups (≤6: 63.8%; &gt; 6–12: 81.7%; &gt; 12: 89.8%). PFS and TTP improved with D + B + TACE vs TACE, regardless of baseline tumor burden, with the best relative improvement in hazard ratios (HRs) in the &gt; 12 group (Table). ORRs were higher for D + B + TACE vs TACE in all groups. Max Grade 3–4 tx-related adverse event (TRAE) frequencies were numerically higher with D + B + TACE vs TACE across tumor burden groups; differences were reduced when adjusted for exposure. No tx-related deaths occurred with D + B + TACE. Conclusions: PFS, TTP, and ORR benefits were seen with D + B + TACE vs TACE with manageable safety, regardless of tumor burden, further supporting a favorable risk-benefit profile with D + B + TACE in embolization-eligible uHCC. Clinical trial information: NCT03778957 . ≤6 &gt;6–12 &gt;12 ITT D + B + TACE n=81 TACE n=82 D + B + TACE n=84 TACE n=95 D + B + TACE n=38 TACE n=28 Median PFS (95% CI), months 19.4(13.7–24.9) 11.1 (7.0–13.6) 13.9 (7.2–19.6) 9.7(6.9–16.3) 11.1 (4.4–16.6) 4.8 (2.9–6.9) PFS HR vs TACE (95% CI) 0.69(0.47–1.01) 0.85(0.59–1.22) 0.61 (0.33–1.13) Median TTP (95% CI), months 22.1(15.1–30.5) 11.1(7.0–13.9) 22.0(13.9–27.7) 15.4(7.2–16.7) 16.6(6.9–25.1) 5.1(3.0–7.1) TTP HR vs TACE (95% CI) 0.60(0.40–0.90) 0.66(0.43–1.01) 0.42(0.20–0.87) ORR, n (%)* 47 (58.8) 27 (33.8) 31 (36.9) 32 (33.7) 10 (26.3) 1 (3.6) SAS n=71 n=81 n=61 n=92 n=22 n=27 Max Grade 3–4 TRAE, n (%) event rate per 100 pt-years 17 (23.9)15.9 9 (11.1)7.9 17 (27.9)19.9 3 (3.3) 3.1 7 (31.8)22.2 0 *In pts with evaluable disease at baseline.

Disitamab vedotin combined with fruquintinib in patients with HER2-expressing or HER2 mutation/amplified metastatic colorectal cancer refractory to at least two standard regimens: A prospective, exploratory, single-arm study.

e15562 Background: Human epidermal receptor growth factor 2 (HER2) -expressing or amplified has been identified in 2-6% of patients with stage III/IV colorectal cancer (CRC).however,there are currently no approved HER2-targeted therapies for CRC in China. Herein, we aimed to investigate the antitumor activity and safety of Disitamab vedotin , a novel humanized anti-HER2 antibody conjugate linked to monomethyl auristatin E via a cleavable linker, in combined with fruquintinib in patients with HER2-expressing or -amplified metastatic colorectal cancer. Methods: In this prospective, exploratory, single-arm study, patients diagnosed pathologically with mCRC, 18-75 years old harboring HER2 expression or HER2 mutation/amplification, and received at least two prior lines of treatment. HER2 expression was defined as animmunohistochemical [IHC]score of 1+, 2+ or 3+, or mutation/amplification identified by NGS. Patients received RC48 2.5mg/kg intravenously every 2 weeks. Meanwhile, fruquintinib was administered orally at 3 mg once daily until disease progression, death, intolerable toxicity, withdrawal of consent. The primary endpoint was ORR ; the secondary endpoints included DCR, PFS, OS and safety. Results: A total of 24 patients were enrolled from Nov 25, 2022 to Dec 16, 2024.HER2 statuses are as follows: 11 patients had IHC 1+ (one of whom had HER2 amplification), 6 had IHC 2+, 4 had IHC 3+, and 3 had HER2 amplification. In the metastatic setting, patients had received a median of 3 prior lines of therapy (range, 2-6). The ORR was 13.6% (3/22) and DCR was 77.3% (17/22). The median PFS was 4.11 months (95% CI: 2.56-5.65) and the median OS was 10.45 months (95% CI: 5.93-13.97). The 9-month OS rate was 55.0%, and the 12-month OS rate was 40.7%. Among the 14 patients with HER2 IHC 2+, IHC 3+ and HER2- amplification, the ORR was 23.1% (3/13), and the DCR was 84.6% (11/13)，the median PFS was 5.78 months (95% CI: 3.33-8.24) and the 9-month OS rate was 66.1%, the 12-month OS rate was 45.3%. 22 (91.7%) patients experienced adverse events , of whom 6 (27.3%) experienced grade 3 TRAEs . The most common grade 3 TRAEs were leukopenia (12.5%), neutropenia (8.3%), hyponatremia (4.2%) and hypokalemia (4.2%). No grade 4 or 5 TRAEs were observed. Additionally, 8 (33.3%) patients required dose reduction. And No patients experienced dose interruption or discontinuation due to TRAEs. Conclusions: The combination of RC48 and fruquintinib has demonstrated promising efficacy and a manageable safety in patients with HER2 -expressing or -amplified mCRC who have failed at least two lines of standard treatments.Patients with HER2 IHC 2+, 3+ and amplification appear to derive greater benefit from this therapeutic regimen. Clinical trial information: NCT05661357 .

Efficacy and safety of HTMC0435 combination with temozolomide in relapsed extensive-stage small-cell lung cancer (ES-SCLC): A phase Ib/II study.

8097 Background: Treatment options for ES-SCLC in second-line setting are limited. HTMC0435, an oral PARP inhibitor, significantly reduced the ability of PARP to repair DNA damage and inhibited tumor cell proliferation when combined with temozolomide (TMZ) in preclinical studies. We investigated the safety and activity of this regimen in relapsed SCLC. Methods: This was a phase Ⅰb/Ⅱ dose-escalation (3+3 design) and dose-expansion study. ES-SCLC patients who had progressed after first- or second-line therapy were eligible. Pts were administered with HTMC0435 6 mg or 8 mg bid on days 1-21 in combination with TMZ 75 mg/m 2 on days 1-7 of each 21-day cycle. The study objectives were to evaluate safety, pharmacokinetics and preliminary efficacy of the combination regimen. Results: From Feb-2023 to Nov-2023, 59 eligible pts were enrolled, with 7 pts in dose escalation and 52 pts in dose expansion. No dose-limiting toxicity (DLT) occurred, and HTMC0435 8mg bid combination with TMZ was selected as recommended phase 2 dose (RP2D). As of 31 October 2024, the median follow-up time was 10.3 months. 55 pts received HTMC0435 8mg bid and TMZ. Among these patients, brain and liver metastases were in 41.8% (23/55) and 23.6% (13/55) pts, respectively. 61.8% (34/55) pts had received prior platinum-based and anti–PD-(L)1 therapy as first line therapy. Among 49 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 24.5% (12/49, 95%CI: 12.0%-37.0%) and 63.3% (31/49, 95%CI: 49.3%-77.3%). The median duration of response (DoR) was 6.9 mos (95%CI: 1.22-12.58). The median progression-free survival (PFS) and overall survival (OS) were 2.8 mos (95%CI: 1.16-4.44) and 12.0 mos (95%CI: 7.85-14.75). 23 pts were platinum-resistant (chemotherapy-free interval &lt; 90 days), with ORR of 25.0% (5/20, 95%CI: 8.7%-49.1%), DCR of 55.0% (11/20, 95%CI: 31.5%-76.9%), mDoR not reached, mPFS of 2.5 mos (95%CI: 1.38-5.03) and mOS of 12.6 mos(95%CI: 5.78-NC). Among the 29 platinum-sensitive pts (chemotherapy-free interval ≥ 90 days), ORR and DCR were 26.9% (7/26, 95%CI: 11.6%-47.8%) and 73.1% (19/26, 95%CI: 52.2%-88.4%), and the mDoR was 4.2 mos (95%CI: 4.14-NC). The mPFS and mOS were 4.2 mos (95%CI: 2.69-5.52) and 11.2 mos (95%CI: 8.38-NC). 96.6% (57/59) pts experienced treatment-related adverse events (TRAEs) and 55.9% (33/59) pts experienced grade 3-4 TRAEs. Most common TRAEs (grade 3-4) were neutropenia (35.6%), leukopenia (28.8%), thrombocytopenia (13.6%), anemia (8.5%). Six (10.2%) pts experienced TRAEs led to dose reduction of HTMC0435 and no TRAEs led to discontinuation of HTMC0435 were reported. Conclusions: This combination of HTMC0435 and TMZ showed promising anti-tumor activity and manageable safety both in platinum-sensitive and platinum-resistant SCLC patients. Clinical trial information: NCT05728619 .

MagnetisMM-32: A phase 3 randomized study of elranatamab vs EPd, PVd, or Kd in patients with relapsed or refractory multiple myeloma (RRMM) and prior anti-CD38–directed therapy.

TPS7568 Background: Elranatamab (ELRA), a BCMA-CD3 bispecific antibody, has shown efficacy and manageable safety as a monotherapy in patients with RRMM. This study will evaluate ELRA monotherapy vs elotuzumab-pomalidomide-dexamethasone (EPd), pomalidomide-bortezomib-dexamethasone (PVd), or carfilzomib-dexamethasone (Kd) in patients with RRMM to determine whether ELRA can provide superior clinical benefit in early relapse (2L+). Methods: MagnetisMM-32 (NCT06152575), a phase 3, open-label, multicenter, randomized study, will enroll ≈492 patients. Patients will receive ELRA (Arm A) or investigator’s choice of EPd, PVd or Kd (Arm B), until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, or study termination. Patients treated with ELRA will receive 2 step-up priming doses followed by weekly doses and subsequently less frequent doses in 28-day cycles. Patients will be randomized 1:1 (stratified by prior line of therapy [1 vs 2 vs 3/4] and International Staging System disease stage [1/2 vs 3]). Key inclusion criteria include age of ≥18 years, prior multiple myeloma diagnosis with measurable disease (per IMWG criteria), evidence of progressive disease or failure to achieve a response to last line of multiple myeloma therapy, 1 to 4 prior lines of therapy including an anti–CD38 antibody–containing regimen (for ≥2 consecutive cycles) and a lenalidomide-containing regimen (for ≥2 consecutive cycles), adequate bone marrow function, and an ECOG performance status of ≤2. Key exclusion criteria include stem cell transplant ≤12 weeks prior to enrollment or active graft vs host disease; active, uncontrolled infection; any other active malignancy &lt;3 yrs prior to enrollment; ongoing grade ≥3 peripheral sensory or motor neuropathy; history of any grade ≥3 peripheral motor polyneuropathy, prior BCMA-directed or CD3-redirecting therapy; never achieved ≥PR with any treatment during disease course; and unable to receive any of the Arm B regimens (EPd, PVd, or Kd). The primary and key secondary endpoints are progression-free survival (PFS) by blinded independent central review (BICR) per IMWG criteria and overall survival (OS), respectively. Other secondary endpoints include PFS and PFS2 (PFS on next line of therapy) by investigator per IMWG, objective response rate, duration of response, very good partial response rate, complete response rate, duration of complete response, and time to response (all by BICR per IMWG), MRD negativity rate (including sustained for ≥12 months) and duration, safety and pharmacokinetics of ELRA, immunogenicity, and health-related quality of life outcomes. The primary endpoint and OS will be compared statistically between treatment arms by stratified log-rank tests. Study funding: Pfizer. Clinical trial information: NCT06152575 .

Transarterial chemoembolization plus donafenib with or without anti-PD-1 antibodies for unresectable hepatocellular carcinoma: A retrospective study.

e16245 Background: Transarterial chemoembolization (TACE) can effectively reduce tumor burden by delivering chemotherapy drugs directly to the tumor while simultaneously blocking its blood supply. Donafenib, a novel multi-kinase inhibitor, showed promise in inhibiting tumor growth and angiogenesis. Combining TACE with donafenib may enhance local and systemic control of unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of TACE combined with donafenib for uHCC patients in a real-world setting. Methods: This single-center, retrospective study was performed from May 2021 to September 2024 at The First Affiliated Hospital of Sun Yat-sen University. Patients diagnosed with uHCC who had received TACE plus donafenib with or without anti-PD-1 antibodies (TACE+Dona or TACE+Dona+PD-1) as the first-line therapy were included. The primary endpoint was progression-free survival (PFS) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and adverse events. Results: In total, 140 consecutively recruited patients were reviewed, 101 of whom were eligible for the study (TACE+Dona, n = 37; TACE+Dona+PD-1, n = 64). Among all patients, median age was 59 years, 89 (88.1%) had HBV, 77 (76.2) had multiple tumors, 62 (61.4%) were at BCLC stage C, 53 (52.5%) presence hepatic venous invasion, median maximum tumor diameter was 7.0 cm (IQR, 4.2-10.2), and median number of TACE sessions per patient was 2 (range, 1-9 sessions). Up to the date of December 30, 2024, the median follow-up was 14.3 months. The median PFS and OS were 10.4 months (95%CI, 8.9-15.7) and 33.5 months (95%CI, 21.4-NA), respectively. The ORR was 72.3%, and DCR was 95.0% (14 of complete response, 59 of partial response, and 23 of stable disease) per mRECIST. Grade 3 or 4 treatment-related adverse events (TRAEs) were observed in 17 (16.8%) patients, and no treatment-related deaths occurred. The most common AEs greater than 10% were hand-foot skin reaction (15.8%), and rash (12.9%). Conclusions: TACE plus donafenib with or without anti-PD-1 antibodies showed encouraging antitumor activity and manageable safety, which maybe a potential regimen option for uHCC.

A TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced cervical cancers with prior anti-PD-(L)1 therapy.

5540 Background: Clinical findings on onatasertib (ATG-008), an oral TORC1/2 inhibitor, showed promising anti-tumor efficacy and manageable safety when used in combination with toripalimab, an anti-PD-1 monoclonal antibody, in treatment-naïve cervical cancer (CC) patients who had not received prior anti-PD-(L)1 therapy. Here, we present results from the anti-PD-(L)1 therapy treated CC cohort of the TORCH-2 study who had at least prior 1 line of anti-PD-(L)1 therapy with the combination of onatasertib and tori. Methods: The TORCH-2 study is a phase 1/2 open-label, dose escalation and expansion trial of onatasertib in combination with tori in patients (pts) with advanced solid tumours (NCT04337463). Eligibility criteria included at least one measurable lesion, ECOG 0-1 and adequate organ function. Pts with prior PI3K/AKT/mTOR inhibitor therapy were excluded. CC pts with at least prior 1 line of anti-PD-(L)1 therapy and 1 line of platinum chemotherapy regardless of PD-L1 expression, were enrolled and received onatasertib 15mg orally once a day (QD) in combination with tori 240 mg, once every 21 days (Q3W). Efficacy assessments were reported based on RECIST1.1 criteria and the endpoints included overall response rate (ORR), disease control rate (DCR), duration of response (DOR), progression free survival (PFS) and overall survival (OS). Results: As of Nov 25, 2024, 30 advanced CC pts who had at least prior 1 line of anti-PD-(L)1 therapy and 1 line of platinum chemotherapy were enrolled. Median age was 56.5 years. Baseline ECOG scores were 0 (26 pts) and 1 (4 pts). There were 14 and 16 pts who had received 1 and ≥2 prior lines of systemic therapy, respectively. Additionally, 16 pts had prior abraxane treatment and 11 pts had prior bevacizumab therapy. The median time since initial diagnosis was 37 months(m). The efficacy-evaluable population (27 CC pts) had an ORR of 22.2% (6/27, all confirmed). The DCR was 85.2%. The median time to response was 1.7 m (1.4, 4.2) and median DOR was 5.7 m (95% CI: 2.7, NE). Median PFS and median OS was 4.2 m (95% CI: 3.3, 5.8) and 21.4 m (95% CI: 15.5, NE), respectively. The ORRs of PD-L1 positive and PD-L1 negative populations were 30% (3/10) and 33.3% (2/6), respectively. Thirty pts (100%) had ≥ 1 TEAEs; 22 (73.3%) pts had grade ≥ 3 TRAEs. The most common all grade TRAEs included hyperglycaemia (56.7%), rash (43.3%) and white blood cell decreased (43.3 %). No TEAE led to death. Conclusions: Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in advanced CC pts with prior anti-PD-(L)1 therapy, regardless of PD-L1 expression. The expansion cohorts are ongoing. Clinical trial information: NCT04337463 .

Neoadjuvant low-dose carboplatin and docetaxel in combination with toripalimab for early or locally advanced triple-negative breast cancer (NeoTOP): A single-arm phase 2 trial.

589 Background: Neoadjuvant immunotherapy combined with chemotherapy improves the rate of pathological complete response (pCR) and prognosis of triple-negative breast cancer (TNBC). However, chemo-immunotherapy treatment is frequently associated with adverse events, resulting in dose reduction and delays. Approaches to deescalate chemo-immunotherapy without compromising outcomes for TNBC patients are needed. Evidence suggests that low-dose carboplatin potentiates the anti-tumor effect of PD-1 inhibitors through many mechanisms. The NeoTOP trial aimed to assess the efficacy and safety of low-dose carboplatin and docetaxel in combination with toripalimab as neoadjuvant therapy for early or locally advanced TNBC. Methods: This is a single-arm, open-label, phase 2 trial. Patients with untreated stage IIA-IIIC TNBC were enrolled. Eligible patients received carboplatin (AUC=4), docetaxel (75 mg/m 2 ) and toripalimab (240 mg), every 21 days for a total of 6 cycles. Toripalimab (240mg, every 3 weeks) continued post-operatively for a further 11 cycles. The primary endpoint was the rate of pCR (ypT0/Tis ypN0). The secondary endpoints included safety, objective response rate (ORR), residual cancer burden (RCB) rate, event-free survival and overall survival. This study used Simon’s two-stage design. Results: From January 2022 to September 2024, 51 patients were enrolled. Among them, 29 patients (56.9%) had stage II, and 22 (43.1%) had stage III. Four patients prematurely discontinued study treatment due to adverse events (three patients) or tumor progression (one patient), including two discontinued toripalimab only and two discontinued both toripalimab and chemotherapy. One of the four patients who discontinued treatment achieved a pCR when proceeding to surgery. One patient achieved clinical CR after neoadjuvant therapy and refused to receive surgery. After surgery, pCR in both breast and lymph nodes was achieved in 29 of 50 patients, resulting in a pCR rate of 58.0%. For all the 51 patients who received at least one dose of neoadjuvant therapy, the ORR was 90.2%. The proportions of RCB-0, RCB-1, RCB-2, and RCB-3 were 58%, 12%, 22%, and 8%. All 51 (100%) patients reported any grade of treatment-related adverse events (TRAEs). Grade ≥3 TRAEs occurred in 23 (45.1%) patients. Serious adverse events were reported in 5 (9.8%) patients. The regimen was well tolerated, and no new toxicity signals were noted. Conclusions: The combination of low-dose carboplatin, docetaxel, and toripalimab showed promising efficacy and manageable safety, suggesting the feasibility of this regimen in the neoadjuvant setting for TNBC. Further randomized phase III trials are warranted. Clinical trial information: NCT06618014 .

SHR-8068 plus adebrelimab and bevacizumab for advanced hepatocellular carcinoma (aHCC): A phase 1b/2 study.

4093 Background: Combination of an anti-PD-1/L1 antibody with an anti-angiogenic agent is currently the preferred 1L treatment for aHCC. Addition of a CTLA-4 inhibitor may further improve anti-tumor activity, with complementary immunostimulatory effects from CTLA-4 and PD-1/L1 blockade. We conducted a multicenter, open-label, phase 1b/2 trial (NCT05444088) to assess SHR-8068, a novel anti-CTLA-4 monoclonal antibody (mAb), combined with adebrelimab (A, anti-PD-L1 mAb) and bevacizumab (B) in patients (pts) with aHCC. Methods: Pts with or without prior treatment were enrolled (phase 1b: failed or refused standard therapy; phase 2: ≤1L systemic therapy, no immunotherapy [IO]). SHR-8068 was evaluated in 2 dosing regimens with AB: 1 mg/kg Q6W (Combo 1) or 4 mg/kg priming dose (Combo 2). An additional cohort evaluated AB alone (Combo 3). A was dosed at 20 mg/kg Q3W and B at 15 mg/kg Q3W for all regimens. Results: As of Oct 31, 2024, a total of 27, 53 and 21 pts received Combo 1, 2, and 3, respectively, across 2 study phases (overall: IO naïve, 97.0%; prior anti-angiogenic therapy, 32.7%); median follow-up was 16.7, 11.1 and 11.3 mo, respectively. In pts treated with Combo 2, the objective response rate (ORR) was 47.2% (25/53; 95% CI 33.3%–61.4%), with a median duration of response (DoR) of 12.7 mo (95% CI 5.8–NR). The median progression-free survival (PFS) was 8.7 mo (95% CI 5.5–11.6); median overall survival (OS) was not reached, with a 12-mo OS rate of 76.0% (95% CI 59.3%–86.6%). Numerically improved ORR and survival outcomes were seen with Combo 2 vs Combo 1 and 3 (Table 1). Overall, grade ≥3 treatment-related adverse events (TRAEs) occurred in 55.6%, 41.5% and 42.9% of pts with Combo 1, 2 and 3. The most common grade ≥3 TRAEs (incidence ≥10% for any Combo) were decreased platelet count (22.2%, 5.7%, and 4.8% for Combo 1, 2, and 3) and hypertension (18.5%, 7.5%, and 9.5%, respectively). TRAE led to discontinuation of any study agent in 11.1%, 1.9% and 9.5% of pts, respectively. There was 1 treatment-related death (Combo 3). Conclusions: SHR-8068 combined with adebrelimab and bevacizumab showed promising efficacy and manageable safety in aHCC. A more favorable benefit-risk profile was observed for SHR-8068 given as a priming dose. A phase 3 trial (NCT06618664) is currently underway to further assess the combination as 1L treatment for aHCC. Clinical trial information: NCT05444088 . Efficacy outcomes. Combo 1 (n=27) Combo 2 (n=53) Combo 3 (n=21) ORR, % (95% CI) 29.6 (13.8–50.2) 47.2 (33.3–61.4) 19.0 (5.5–41.9) Median DoR * , mo (95% CI) NR (9.4–NR) 12.7 (5.8–NR) NR (7.0–NR) 9-mo DoR rate * , % (95% CI) 100.0 (NR–NR) 69.8 (41.7–86.3) 66.7 (5.4–94.5) DCR, % (95% CI) 77.8 (57.7–91.4) 77.4 (63.8–87.7) 81.0 (58.1–94.6) Median PFS * , mo (95% CI) 6.9 (2.7–NR) 8.7 (5.5–11.6) 6.7 (2.8–9.5) 12-mo OS rate * , % (95% CI) 70.4 (49.4–83.9) 76.0 (59.3–86.6) 70.8 (46.2–85.7) Tumor response was assessed by investigator per RECIST v1.1. * Kaplan-Meier method. NR, not reached.