4579 Background: SYS6002 is a next-generation Nectin-4-targeting antibody-drug conjugate (ADC) utilizing a novel site-specific enzymatic conjugation technology to link monomethyl auristatin E (MMAE) with a uniform drug-antibody ratio of 2. This design aims to enhance linker stability, minimize free payload release, and improve the therapeutic window. Methods: This phase 1 study (ChiCTR2200066256) included dose escalation (0.2–4.5 mg/kg Q3W; 2.4–2.7 mg/kg Q2W), pharmacokinetic (PK) expansion, and cohort expansion phases. Eligible patients had advanced solid tumors refractory to standard therapies. The primary endpoints were safety and recommended phase 2 dose (RP2D). Secondary endpoints included PK profile and efficacy, with the latter reported herein were specific to the pretreated advanced urothelial carcinoma (aUC) cohort. Results: As of Dec 19, 2025, 150 patients were enrolled (dose escalation n=32; PK expansion n=70; cohort expansion n=48). The maximum tolerated dose was not reached up to 4.5 mg/kg. The RP2D in aUC patients was determined as 3.6 mg/kg Q3W. SYS6002 exhibited a manageable safety profile in all 150 patients. With a median follow-up of 11.5 months (IQR 6.5-15.5), 2 (1.3%) patients discontinued treatment due to treatment-related adverse events (TRAEs) and no TRAE led to death. The most common TRAEs were ocular disorders (e.g., corneal disorder, dry eye), which were predominantly Grade 1-2. While ocular events were frequent (consistent with on-target effects), they were reversible and effectively managed with prophylaxis, resulting in no treatment discontinuations due to ocular toxicity. Notably, TRAEs typically associated with payload shedding were characterized by low incidence, with peripheral neuropathy reported in 11.3% of patients (no Grade ≥3) and rash in 20.7% (2.0% Grade ≥3), which compared favorably to historical data of other MMAE-based ADCs. Furthermore, no Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis reported. In 85 efficacy-evaluable aUC patients across all tested doses, the objective response rate (ORR) was 37.6% (95%CI 27.4-48.8) and disease control rate (DCR) was 77.6% (95%CI 67.3-86.0), with a median duration of response of 6.2 months (95%CI 4.3-10.4) and median overall survival of 13.2 months (95%CI 10.6-14.9). At the RP2D (n=39), the ORR reached 41.0% (95%CI 25.6-57.9). Encouragingly, in heavily pretreated patients with prior MMAE-based ADC exposure (n=25), SYS6002 maintained activity with an ORR of 24.0% (95%CI 9.4-45.1) and DCR of 72.0% (95%CI 50.6-87.9), suggesting potential to overcome resistance. Conclusions: SYS6002 demonstrated a distinct safety profile from other Nectin-4 ADCs. Its promising efficacy in aUC patients, extending to those progressing on prior MMAE-based ADCs, supports further phase 3 trials. Clinical trial information: ChiCTR2200066256.

Sushi domain-containing protein 2 (SUSD2) is a transmembrane protein with context-dependent roles in cancer, but its function and mechanism in colorectal cancer (CRC) remain unclear. This study aimed to investigate the role of SUSD2 in CRC progression and its underlying molecular mechanism. Analysis of TCGA dataset revealed that SUSD2 was significantly downregulated in CRC tissues, and low SUSD2 expression correlated with poor patient survival. Functional experiments demonstrated that SUSD2 overexpression suppressed CRC cell proliferation, migration, and invasion, promoted apoptosis in vitro, and inhibited tumor growth in a xenograft mouse model. Mechanistically, SUSD2 activated the NF-κB pathway, leading to p65 nuclear translocation and transcriptional upregulation of NOX4, which induced lethal oxidative stress characterized by increased reactive oxygen species, malondialdehyde, and mitochondrial superoxide. Knockdown of NOX4 rescued SUSD2-mediated phenotypic effects, and pharmacological inhibition of NF-κB abrogated SUSD2-induced NOX4 upregulation, confirming that NOX4 functions downstream of NF-κB in this axis. Collectively, these findings establish SUSD2 as a tumor suppressor in CRC and an independent prognostic biomarker. The SUSD2/NF-κB/NOX4 axis represents a critical regulatory pathway that constrains CRC progression and offers a potential therapeutic vulnerability.

3026 Background: Treatment options in China are limited for patients with late-line, HER2-expressing advanced solid tumors. In Part 1 of DESTINY-PanTumor02, T-DXd showed clinically meaningful antitumor activity in HER2-expressing advanced solid tumors, with the greatest benefit observed in HER2 IHC 3+ tumors. Based in part on these findings, T-DXd has been approved in multiple countries worldwide, including the US, as treatment for patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and/or have no satisfactory alternative therapies. Following the results from DESTINY-PanTumor02, DESTINY-PanTumor03 is evaluating T-DXd in patients in China with HER2-expressing advanced solid tumors. The primary analysis of Part 1 of DESTINY-PanTumor03 is presented here. Methods: DESTINY-PanTumor03 is an open-label, Phase 2 study (NCT06271837). Part 1 is evaluating T-DXd (5.4 mg/kg IV Q3W) in patients in China with HER2 IHC 3+ (by central testing), locally advanced, unresectable, or metastatic solid tumors (excluding breast and gastric cancers) after ≥1 prior systemic treatment for advanced disease or without treatment options. The primary endpoint is confirmed objective response rate (ORR) by independent central review (ICR) per RECIST 1.1. Secondary endpoints include ORR by investigator assessment (INV) per RECIST 1.1; duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) by INV and ICR per RECIST 1.1; overall survival (OS); and safety. Results: At primary analysis data cutoff (November 28, 2025), 50 patients with biliary tract (n = 11), colorectal (n = 6), cervical (n = 10), endometrial (n = 7), ovarian (n = 5), non-small cell lung (n = 7), or other cancers (n = 4) had received T-DXd. Median follow-up duration was 9.9 (range 1.1–18.3) months. Median number of prior treatment regimens was 2 (range 1–10). By ICR, ORR (95% CI) was 58.0% (43.2, 71.8), median DOR (95% CI) was 15.4 (12.5, not evaluable [NE]) months, DCR (95% CI) at Week 6 was 88.0% (75.7, 95.5), and median PFS (95% CI) was 15.7 (7.2, NE) months. By INV, ORR (95% CI) was 56.0% (41.3, 70.0). Median OS was not reached. Grade ≥3 drug-related adverse events occurred in 31 (62.0%) patients, and adjudicated drug-related interstitial lung disease / pneumonitis occurred in 4 (8.0%) patients (Grade 2 n = 3 [6.0%], Grade 3 n = 1 [2.0%]). Conclusions: T-DXd demonstrated durable and clinically meaningful antitumor activity in pretreated patients in China with HER2 IHC 3+ advanced solid tumors. Safety was generally consistent with the established T-DXd profile. Results from DESTINY-PanTumor03 Part 1 support T-DXd as a tumor-agnostic treatment for patients in China with HER2 IHC 3+ solid tumors. Clinical trial information: NCT06271837 .

BACKGROUND:Efficacy of second-line treatments after first-line platinum-based chemotherapy in advanced cervical cancer is modest. This open-label, single-arm, multicentre, proof-of-concept phase 2 study evaluated fruquintinib plus sintilimab in advanced cervical cancer. METHODS:Patients recruited between July 2021 and June 2022 had received at least first-line platinum-based chemotherapy or were unable to receive standard treatment in China. Patients received fruquintinib 5 mg once daily orally (2 weeks on/1 week off) plus sintilimab 200 mg intravenously every 3 weeks. Efficacy and safety analyses included patients who had received at least one dose of study drug. RESULTS:Here we show the results of 34 patients who received treatment; 28 (82%) have prior systemic antitumour therapy, with 19 (68%) pretreated patients having programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1. The objective response rate (ORR) is 32% (95% confidence interval [CI] 17-51), meeting the prespecified effective boundary, and the disease control rate (DCR) is 97% (95% CI 85-100). Median progression-free survival (PFS) and overall survival (OS) are 8.3 months (95% CI 5.5-19.4) and 23.5 months (95% CI 15.8-not estimable [NE]), respectively. The most common grade ≥ 3 treatment-related adverse event is palmar-plantar erythrodysaesthesia syndrome (21%). In pretreated patients with PD-L1 CPS  ≥ 1, ORR is 37% (95% CI 16-62), median PFS is 19.4 months (95% CI 4.0-22.1), and OS rate at 18 months is 72% (95% CI 46-87). CONCLUSIONS:Fruquintinib plus sintilimab may indicate favourable and durable antitumour activity with a manageable safety profile in advanced cervical cancer, especially in pretreated patients with PD-L1 CPS ≥1, warranting further investigation.

5512 Background: BAT8006 is a folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), while BAT1308 is a recombinant humanized anti-PD-1 monoclonal antibody. Both agents have individually demonstrated acceptable tolerability and promising antitumor activity in solid tumors. Herein, we report a phase Ib/II trial designed to evaluate the safety and efficacy of BAT8006 in combination with BAT1308 for patients with advanced endometrial cancer. Methods: Eligible patients included those with pathologically confirmed endometrial cancer who had experienced disease recurrence or progression following at least 1 line of platinum-based chemotherapy or immunotherapy-based regimen, with no more than 3 prior lines of systemic therapy. Enrolled patients received BAT8006 (76 mg/m² or 84 mg/m²) in combination with BAT1308 (fixed dose of 300 mg) every 3 weeks until disease progression, intolerable toxicity, or other protocol-specified reasons. The primary endpoints were safety and ORR as assessed by investigators per RECIST v1.1. Results: As of December 25, 2025, a total of 45 patients with advanced endometrial cancer were enrolled in this study. The median age of the cohort was 62 years (range, 27–75 years). Among these patients, 80.0% had ECOG PS of 0, and 80.0% presented with metastatic disease at baseline. All patients had received prior platinum-based chemotherapy; additionally, 48.9% had undergone prior immunotherapy, and 15.6% had received two or more prior lines of systemic therapy. The proportion of patients with FRα positivity (defined as FRα expression ≥1%) was 62.2%. TRAEs were reported in 41 patients (91.1%). Grade ≥3 (G3) TRAEs occurred in 24 patients (53.3%), and SAEs were observed in 17 patients (37.8%). The most common TRAEs (incidence ≥20%) included leukopenia (77.8%), anemia (77.8%), neutropenia (62.2%), nausea (55.6%), thrombocytopenia (53.3%), vomiting (48.9%), lymphopenia (35.6%), pyrexia (26.7%), decreased appetite (26.7%), increased alanine aminotransferase (22.2%), and asthenia (22.2%). No cases of interstitial lung disease were reported. IrAEs occurred in 3 patients (6.7%). TRAEs resulted in dose reduction in 10 patients (22.2%) and treatment discontinuation in 2 patients (4.4%). No treatment-related deaths were recorded. Efficacy was evaluable in 34 patients. The overall ORR was 38.2% (95% CI: 22.2–56.4), and DCR was 70.6% (95% CI: 52.5–84.9). In the BAT8006 (76 mg/m²) + BAT1308 cohort, ORR was 44.4% (95% CI: 21.5–69.2) and DCR was 72.2% (95% CI: 46.5–90.3). In the BAT8006 (84 mg/m²) + BAT1308 cohort, ORR was 31.3% (95% CI: 11.0–58.7) and DCR was 68.8% (95% CI: 41.3–89.0). Conclusions: These findings suggest that BAT8006 in combination with BAT1308 may represent an effective therapeutic strategy for advanced endometrial cancer, with a manageable safety profile. Further prospective studies are warranted to validate the efficacy and safety of this combination regimen. Clinical trial information: CTR20242449.

5627 Background: SSGJ-707 is a fully human immunoglobulin G4 bispecific antibody targeting programmed death 1 (PD-1) and vascular endothelial growth factor (VEGF). SSGJ-707 has demonstrated promising efficacy and manageable safety alone and in combination with chemo in phase 2 studies in solid tumors. We report results from the phase 2 SSGJ-707-ST-II-02 study (NCT06522828) of 1L SSGJ-707 + chemo in advanced/recurrent EC. Methods: Pts with newly diagnosed stage lIl/IV or recurrent EC with low potential for cure by radiation therapy (tx) or surgery and systemic tx-naive were enrolled. Pts received SSGJ-707 5 mg/kg or 10 mg/kg Q3W + chemo (carboplatin AUC 5 + paclitaxel 175 mg/m 2 ) Q3W for 6 cycles, followed by SSGJ-707 maintenance tx until loss of clinical benefit or intolerable toxicity for up to 2 years. Primary endpoints were safety and ORR (RECIST 1.1). Secondary endpoints include duration of response (DOR), PFS, OS, PK, and biomarkers. Results: At data cutoff (Nov 28, 2025), 32 pts with EC (26 mismatch repair proficient [pMMR], 6 MMR deficient [dMMR]) received 5 mg/kg (n=16) or 10 mg/kg (n=16) SSGJ-707 + chemo. Median SSGJ-707 tx duration was 5.6 mo (range, 0.2-13.6); 8 pts (25.0%) discontinued tx. In the evaluable population, confirmed ORR was 85.7% (12/14 pts) for the 5 mg/kg dose and 80.0% (12/15) for the 10 mg/kg dose. Results for pMMR and dMMR groups are in the Table. Median PFS, OS, and DOR were not reached for either dose. Any-grade tx-related adverse events (TRAEs) were reported in 30/32 pts (93.8%) and grade ≥3 TRAEs in 22/32 pts (68.8%). The most common TRAEs (≥40%) included neutrophil count decreased (59.4%), white blood cell count decreased (59.4%), anemia (56.3%), and platelet count decreased (56.3%). No TRAEs led to death. TRAEs led to discontinuation of SSGJ-707 in 2 pts (6.3%). Immune-related AEs occurred in 6 pts (18.8%): hypothyroidism (n=4), hyperthyroidism (n=3), and rash (n=2). VEGF-related AEs occurred in 13 pts (40.6%): blood pressure elevation (n=6), proteinuria (n=6), hemorrhage (urinary occult blood positive; n=2), perforation and fistula (n=2), and venous thrombosis (n=1). Conclusions: SSGJ-707 + chemo demonstrated promising efficacy with a manageable safety profile in pts with tx-naive advanced/recurrent EC, supporting further investigation of SSGJ-707 in these pts. Clinical trial information: NCT06522828 . 5 mg/kg Q3W (n=14) 10 mg/kg Q3W (n=15) pMMR (n=12) dMMR (n=2) pMMR (n=11) dMMR (n=4) Confirmed ORR, n (%) [95% CI] 10 (83.3) [51.6, 97.9] 2 (100)[15.8, 100.0] 9 (81.8)[48.2, 97.7] 3 (75.0)[19.4, 99.4] Complete response 0 0 1 (9.1) 0 Partial response 10 (83.3) 2 (100) 8 (72.7) 3 (75.0) Stable disease 2 (16.7) 0 2 (18.2) 1 (25.0) Progressive disease 0 0 0 0 CR/PR pending – – 1 a 1 Unconfirmed ORR, n (%) [95% CI] 10 (83.3) [51.6, 97.9] 2 (100)[15.8, 100.0] 10 (90.9)[58.7, 99.8] 4 (100)[39.8, 100.0] a One additional pt in the 10 mg/kg group confirmed in Dec.

e17612 Background: FRUSICA-1(NCT03903705) is an open label, single-arm, pivotal phase II study, demonstrated the promising efficacy and favorable safety of fruquintinib (F) + sintilimab (S) in previously treated advanced EMC patients (pts) with pMMR status, with objective response rate (ORR): 35.6%; median progression-free survival (mPFS): 9.5mo; median overall survival (mOS): 21.3mo (Wu X, et al; 2024 ASCO). PPES and hypothyroidism are two common adverse events in the combination therapy of angio-genesis tyrosine kinase inhibitors and PD-1 antibody. Researches have indicated patients with PPES may experience better treatment outcomes in various cancer types. Immune related adverse events (irAE) were also deemed as predictor of response in gynecologic cancers. Therefore, we launched a subgroup analysis of the treatment outcome in patients who developed PPES or hypothyroidism in FRUSICA-1. Methods: EMC pts with centrally confirmed pMMR status who progressed after ≤ 2 platinum-based systemic therapy were treated with F (5mg QD orally, 2w on/1w off) + S (200mg IV, Q3W), in a 3-week cycle until disease progression or unaccepted toxicity. Patients who developed PPES or hypothyroidism were extracted and the efficacy analysis was then conducted accordingly. Results: As of 15th May 2024, 98 eligible pts were enrolled and evaluated with a median follow-up of 22.0 mo (95%CI: 20.5, 23.7). In the full analysis set (FAS), 38 (38.8%) pts experienced PPES, 45 (45.9%) experienced hypothyroidism. Assessed by independent review committee (IRC), Patients who developed PPES showed numerically higher efficacy with an ORR 47.4% (95% CI: 31.0, 64.2), DCR 92.1% (95% CI: 78.6, 98.3), mPFS and mOS not reached (NR), 15-mo PFS rate 60.7% (95% CI: 39.3, 76.6), 24-mo OS rate 59.3% (95% CI: 40.5, 73.9). Patients who had irAE hypothyroidism, also showed a higher efficacy, with an ORR 44.4% (95% CI: 29.6, 60.0), DCR 93.3% (95% CI: 81.7, 98.6), mPFS 16.6 mo (95% CI: 6.9, 27.4), mOS 24.0 mo (95% CI: 17.7, NR), the maturity of PFS and OS were 53.3% (24/45) and 46.7% (21/45). Conclusions: In FRUSICA-1 study, PPES and irAE hypothyroidism may be associated with higher ORR, longer PFS and OS in advanced EMC patients. PPES and irAE hypothyroidism could potentially be predictive of clinical outcomes for pts with treatment with fruquintinib plus Sintilimab. Clinical trial information: NCT03903705 .

3037 Background: DM002 is a bispecific ADC (BsADC) conjugated to BLD1102, a linker/payload system composed of a linker and a DNA topoisomerase I inhibitor (BCPT02), targeting MUC1 and HER3 with an average DAR value of 8. MUC1 and HER3 are highly co-expressed in several types of solid tumors, for which DM002 has demonstrated robust anti-tumor activity in PDX/CDX models. Methods: This is a First-in-human dose-escalation study (NCT06751329). Patients (pts) with advanced solid tumors received DM002 by IV administration from 1 to 6.0 mg/kg Q3W. The classical “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Tumor response was evaluated by the Investigators based on RECIST v 1.1. A Safety Monitoring Committee (SMC) was established to determine the dose levels, dose regimen, and the maximum tolerated dose (MTD)/ recommended dose for expansion (RDE). Results: As of 28 Dec 2025, a total of 29 pts from China, United states of America and Australia were enrolled and received ≥1 dose of DM002 across 5 dose cohorts. Median age was 61 years (range 45-80). Baseline ECOG scores were 0 (n=8), 1 (n=21) with all pts progressed after an average of 2.5 (range 1-5) prior lines of available standard therapy. There were three dose-limiting toxicities observed in 2 patients at 6.0 mg/kg. The MTD is 4.5mg/kg. Nineteen pts (65.5%) experienced treatment-related adverse events (TRAEs), mainly manifested as hematological toxicity and gastrointestinal reactions. the most common TRAEs (≥15%) including: nausea (37.9%), neutropenia (37.9%), thrombocytopenia (34.5%), anemia (31%), vomiting (27.6%), leukopenia (20.7%), hyponatremia (20.7%), diarrhea (17.2%), alanine aminotransferase increased (17.2%), hypoalbuminemia (17.2%). Most TRAEs were Grade 1-2 and Grade ≥3 TRAEs reported in 12 pts (9 neutropenia, 5 leukopenia, 4 thrombocytopenia, 3 anemia, 2 lymphocytopenia, hyponatremia and febrile neutropenia, 1 aspartate aminotransferase increased, blood bilirubin increased, monocyte count decreased, myelosuppression, hypocalcemia, malaise and infection). No ILD was observed. Among 15 pts having imaging tumor assessment by RECIST v1.1, there were 3 PRs, including 1 pt with prostate cancer and 1pt with ovarian cancer at 3.0 mg/kg, and 1 pt with pancreatic cancer at 4.5 mg/kg, and 8 pts with stable disease (SD). In the 3.0/4.5/6.0 mg/kg dose groups, a total of 8 pancreatic pts underwent imaging tumor assessment, with 1 pt achieving PR, and 5 pts achieving stable disease (SD). Conclusions: DM002 is safe and tolerable up to 4.5 mg/kg dose level. In pancreatic cancer, prostate cancer and ovarian cancer, DM002 has demonstrated an encouraging efficacy with a manageable safety profile. The putative RDEs are 3.0 and 3.5 mg/kg which will be further evaluated in phase II trials. Clinical trial information: NCT06751329 .

Although poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and bevacizumab were approved as first-line maintenance for advanced ovarian cancer (OC), evidence comparing this combination with PARPi monotherapy, especially in BRCA-mutated/homologous recombination-deficient (HRD) patients, is lacking. This study compared combined fuzuloparib (a PARPi) plus apatinib (a vascular endothelial growth factor receptor-2 inhibitor) with either fuzuloparib or placebo as first-line maintenance in patients with advanced OC. Patients who had newly diagnosed, advanced OC and responded to first-line, platinum-based chemotherapy were randomized 2:2:1 to receive combined fuzuloparib (100 mg twice daily) plus apatinib (375 mg daily), fuzuloparib (150 mg twice daily) plus placebo, or double-placebo treatment. The primary end point was blinded independent review committee (BIRC)-assessed progression-free survival (PFS). Six hundred seventy-four patients were randomized to receive fuzuloparib plus apatinib (n = 269), fuzuloparib (n = 269), or placebo (n = 136). At the final analysis (November 1, 2024; 385 BIRC-assessed PFS events; median follow-up, 40 months), the median BIRC-assessed PFS was 26.9 months with the combination versus placebo (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.75; one-sided p < .0001) and 29.9 months with fuzuloparib monotherapy versus placebo (HR, 0.58; 95% CI, 0.44-0.75; one-sided p < .0001) compared with 11.1 months with placebo. A PFS benefit was observed regardless of germline BRCA1/2 mutation status. In homologous recombination-deficient patients (including those with BRCA1/2 mutations), combined fuzuloparib and apatinib produced a PFS similar to that of fuzuloparib (34.1 vs. 35.8 months, respectively); in homologous recombination-proficient patients, PFS had a trend favoring the combination (16.6 vs. 11.0 months; HR, 0.73; 95% CI, 0.45-1.19). Both treatments were well tolerated. Overall survival was immature. Both fuzuloparib and combination therapy improved PFS compared with placebo as maintenance therapy for patients who had newly diagnosed, advanced OC. Adding apatinib to fuzuloparib did not prolong PFS among homologous recombination-deficient patients. There was a PFS benefit trend among homologous recombination-proficient patients who received combination therapy compared with those who received monotherapy.

3003 Background: T-Bren is a HER2-directed antibody-drug conjugate (ADC) consisting of an anti-HER2 monoclonal antibody linked to a potent topoisomerase I inhibitor (Ed-04). In phase I studies, T-Bren demonstrated encouraging anti-tumor activity with a manageable safety profile in patients (pts) with solid tumors. Results of safety/efficacy from two phase II studies in pts with R/M ovarian cancer (OC) are presented. Methods: Two studies evaluated T-Bren as monotherapy in pts with R/M platinum-resistant (disease progression within 6 months of the last dose of platinum-based chemotherapy) and platinum-sensitive OC. Pts with R/M OC were treated at 3.8mg/kg or 4.4mg/kg D1 Q3W. Primary endpoints include ORR and RP2D. Pts were selected for HER2 expression (ultra-low/1+/2+/3+). Results: As of Nov 30, 2025, a total of 65 pts were enrolled at 3.8 (N = 51), or 4.4mg/kg (N = 14) D1Q3W. Of all pts, 28 (43.1%) pts previously received ≥3 lines of therapy. The most common grade 3 and above hematologic TRAEs were thrombocytopenia (41.5%), leukopenia (35.4%), neutropenia (35.4%), and anemia (29.2%); the most common grade 3 and above non-hematologic TRAEs were asthenia (6.2%), lymphocyte count decrease (6.2%). Grade 3 and above TRAEs, which were predominantly hematologic in nature, were able to be effectively managed with standard supportive measure including dose reductions, as demonstrated by the TRAE leading to discontinuation rate of 3.1%. No ILD was observed. No new safety signals were identified. Median follow-up was 7.8 mo. Among pts at 3.8mg/kg D1 Q3W, confirmed ORR (cORR) was 88.9% in platinum-sensitive OC and 47.5% in platinum-resistant OC. mPFS had not reached and 9-mo PFS rate was 85.7% in platinum-sensitive OC and 61.2% in platinum-resistant OC. Efficacy results are summarized in the table below. Conclusions: T-Bren has demonstrated promising anti-tumor activity with a manageable safety profile in heavily pre-treated pts with R/M OC. Dose 3.8mg/kg D1 Q3W was chosen as the RP3D. Phase III study of platinum-resistant OC is in preparation. Clinical trial information: NCT06031584; NCT06131450 . Total (N=63) 3.8mg/kgTotal (N=49) 3.8mg/kgPlatinum-sensitive (N=9) 3.8mg/kgPlatinum-resistant(N = 40) Median prior LoT (range) 2 (1-8) 2 (1-6) 2 (1-4) 2 (1-6) ORR, % (95% CI) 57.1 (44.0, 69.5) 59.2 (44.2, 73.0) 88.9 (51.8, 99.7) 52.5 (36.1, 68.5) cORR, % (95% CI) 49.2 (36.4, 62.1) 55.1 (40.2, 69.3) 88.9 (51.8, 99.7) 47.5 (31.5, 63.9) DCR, % (95% CI) 88.9 (78.4, 95.4) 89.8 (77.8, 96.6) 100 (66.4, 100) 87.5 (73.2, 95.8) mPFS (mo) (95% CI) 9.3 (7.0, NR) NR (7.0, NR) NR (5.6, NR) NR (7.0, NR) 9-mo PFS rate, % (95% CI) 50.1 (24.0, 71.6) 67.5 (46.0, 81.9) 85.7 (33.4, 97.9) 61.2 (34.5, 79.7) *All pts who received at least one dose of T-Bren, excluding those still ongoing with insufficient follow up were used for efficacy analysis.

In the SCORES study ( NCT04908787 ), women with ovarian cancer that progressed within 6 months after completing platinum-based therapy were randomized (2:1) to receive suvemcitug (1.5 mg kg−1), an antibody to vascular endothelial growth factor or placebo every 2 weeks, with chemotherapy (paclitaxel, topotecan or PEGylated liposomal doxorubicin). The primary endpoint was progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate, disease control rate, duration of response, quality of life, safety, pharmacokinetics and antidrug antibodies. Between June 5, 2021 and October 11, 2024, 421 participants were randomized (49.4

The phase 3 COMPASSION-16 trial demonstrates significant progression-free survival (PFS) and overall survival (OS) benefits with cadonilimab plus standard therapy in patients with persistent, recurrent, or metastatic cervical cancer. This analysis aims to assess efficacy outcomes in patient subgroups of COMPASSION-16. The dual primary endpoints of COMPASSION-16 are PFS, assessed by the blinded independent central review (BICR) according to RECIST version 1.1, and OS. The secondary endpoint is objective response rate. In this subgroup analysis, the PFS, OS and objective response rate are evaluated in subgroups including bevacizumab use, prior concurrent chemoradiotherapy, PD-L1 combined positive score (CPS), metastatic disease at baseline, platinum use, and age. With median follow-up of 25.6 months, hazard ratios (HRs) for PFS favour cadonilimab group in all subgroups. Moreover, the addition of cadonilimab is also associated with prolonged overall survival. This subgroup analysis confirms that improvements in progression-free and overall survival are consistent with the primary results of the COMPASSION-16 study across diverse patient profiles.

Recent breakthroughs highlight a previously underappreciated role of the nervous system in tumor biology, drawing attention to the emerging interdisciplinary field of tumor neuroscience. Foundational discoveries have elucidated complex bidirectional interactions between neurons and cancer cells, redefining the tumor microenvironment as a dynamic neurobiological niche. A major recent breakthrough is the discovery that tumor cells can form direct synaptic or pseudo-synaptic contacts with neurons, extending the concept of synaptic communication beyond the nervous system. In this Review, we summarize current knowledge of neuronal regulation in cancer across three layers: direct synaptic communication, neuron-derived paracrine signaling, and neuroimmune modulation. We further discuss the functional consequences of these interactions, including perineural invasion, tumor-associated epilepsy and cancer pain, together with emerging therapeutic strategies targeting tumor-neuron crosstalk, highlighting these overlooked therapeutic opportunities for highly aggressive tumors. Finally, we propose a translational framework to bridge basic discoveries with clinical application.