Background Therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) after first-line failure remain limited, particularly in patients previously exposed to immune checkpoint inhibitors (ICIs). We evaluated the efficacy, safety, and exploratory biomarker correlates of camrelizumab, an ICI, combined with nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, as second-line therapy for ESCC. Methods In this multicenter, single-arm, phase II study, patients with advanced ESCC who progressed after first-line therapy received camrelizumab (200 mg every 2 weeks) plus nimotuzumab (400 mg weekly). The primary endpoint was the objective response rate (ORR). Results Between November 2021 and December 2024, 46 patients were enrolled. The confirmed ORR was 32.6% (15/46; 95% CI 19.5 to 48.0) and the disease control rate was 82.6% (38/46; 95% CI 68.6 to 92.2). Median progression-free survival (PFS) was 9.13 months (95% CI 5.95 to 9.76), and median overall survival (OS) was 12.62 months (95% CI 9.40 to 15.01). Clinical activity was observed across subgroups, including immunotherapy-naïve and previously treated patients (ORR 32.0% vs 33.3%). Patients with EGFR amplification demonstrated a higher ORR (47.1% vs 24.0%) and longer median OS (13.17 vs 9.99 months). Among patients with M1 disease (n=39), the ORR was 30.8% (95% CI 17.0 to 47.6), the median PFS was 8.48 months (95% CI 5.95 to 9.59), and the median OS was 12.55 months (95% CI 7.95 to 14.88). Treatment-related adverse events occurred in 80.4% of patients, with grade ≥3 events in 8.7%. Exploratory analyses suggested that MUC16 mutations were associated with lower ORR (8.3% vs 46.4%, p=0.030), NOTCH3 mutations with prolonged survival (median PFS not reached vs 8.21 months, HR 0.20, p=0.015; median OS not reached vs 10.58 months, HR 0.22, p=0.026), and MTAP deletions with shorter PFS (3.71 vs 9.49 months, HR 3.18, p=0.005). Conclusions Camrelizumab combined with nimotuzumab demonstrated encouraging antitumor activity and a manageable safety profile as second-line therapy for advanced ESCC. Trial registration number NCT03766178 .

Small cell carcinoma of the esophagus (SCCE) is both rare and aggressive. Lacking its own guidelines, it has historically been managed with treatment models borrowed from small cell lung cancer (SCLC). However, advances in multi-omics and immunology are beginning to uncover distinct molecular and immune features in SCCE. These include frequent alterations in NOTCH1 and PTEN, ASCL1 and NEUROD1 transcriptional programs, and a highly adaptive immunosuppressive tumor microenvironment. Together, they point to unique biological traits that may be targetable. Clinically, conventional chemotherapy, radiotherapy, and surgery are being reassessed, with neoadjuvant therapy showing increasing value. Mechanism-driven strategies such as anti-angiogenic and DLL3-targeted therapies are under active exploration. At the same time, emerging biomarkers and multimodal predictive models are offering new tools for risk stratification and personalized management. Yet pathology adds further challenges: boundaries between SCCE, squamous cell or adenocarcinomas with neuroendocrine differentiation, and mixed or collision tumors remain blurred, creating diagnostic and therapeutic uncertainty. These challenges highlight an important shift-SCCE is no longer a clinical "black box" but rather a frontier that demands resolution through a translational lens. By realigning fragmented basic research with clinical evidence, this review not only presents a comprehensive picture of SCCE but also aims to provide clear therapeutic direction for this malignancy.

3032 Background: EGFR and c-Met overexpression are common across various solid tumors. TQB6411 is a novel ADC binding to both EGFR and c-Met with a valency of 1:2 to enhance the affinity to c-Met. Here we report the preliminary results of this first-in-human phase 1 study of TQB6411(NCT07043751). Methods: Patients (pts) with advanced malignant tumor who had failed or were intolerant to standard treatment were eligible. TQB6411 was administered intravenously once every 3 weeks. An accelerated titration design was used for the initial dose level (0.8 mg/kg), followed by a conventional 3+3 dose escalation design for the remaining dose levels. The primary endpoints were dose-limiting toxicity (DLT), recommended phase II dose and safety. Results: As of December 31, 2025, 26 pts were enrolled and received research treatment (median age [range], 60[33–75] years; 46.2% female). The most common diagnosis was non-small cell lung cancer (NSCLC, 21 pts), followed by esophageal cancer (EC, 3 pts) and colorectal cancer (CC, 2 pts). All pts had received at least one previous line of systemic treatment. Dose group assignments were as follows: 1 in 0.8mg/kg, 3 in 2.4mg/kg, 13 in 4mg/kg, 6 in 5.3mg/kg, and 3 in 6.6mg/kg. By the data cutoff date of January 9, 2026, the dose had been escalated to 6.6mg/kg, with no DLT occurring. The median treatment duration was 3 cycles (rang:1-9). In 22 pts who were followed up for at least 21 days, 19 (86.4%) experienced at least 1 treatment-related adverse event (TRAE). The most common TRAEs included asthenia (54.5%), infusion reaction (50.0%, decreasing to 38.9% in the ≥4 mg/kg dose group after prophylaxis modification), myalgia (27.3%), alopecia (22.7%), and neutrophil count decreased (22.7%). No interstitial lung disease occurred. Only 4 cases of grade 3 AEs (two of neutrophil count decreased, one of allergic shock, one of white blood cell count decreased) were observed in 3 pts and were all attributed to TQB6411. No ≥ grade 4 AEs occurred. In the ≥4 mg/kg dose group, 8 pts received at least one imaging assessment, 4 achieved a partial response (PR), giving an objective response rate of 50.0%. The disease control rate was 100%. The details of efficacy results are shown in the table below. Conclusions: In this ongoing phase 1 study. TQB6411 showed an impressive safety profile, with a lower incidence of higher-grade TRAEs (especially lower haematological toxicities), and encouraging efficacy, with tumor responses could be observed even in the relatively lower dose group. Clinical trial information: NCT07043751 . 4mg/kg (N = 6) 5.3mg/kg (N=2) PR, n 3 (NSCLC: 2, EC:1) 1(NSCLC) SD, n 3 (NSCLC) 1 (NSCLC)

Objective:PD-1 monoclonal antibodies are cornerstone therapies for advanced malignant melanoma, yet treatment response varies greatly between patients. This study investigated temporal changes in peripheral blood inflammatory and nutritional parameters during PD-1 therapy, examined their associations with clinical outcomes, and identified prognostic biomarkers. Methods:A retrospective analysis was conducted on 99 patients with advanced malignant melanoma who received PD-1 monoclonal antibody treatment at the First Affiliated Hospital of Zhengzhou University (January 2019-September 2024). Imaging evaluations (CT/MRI, with PET-CT for suspected distant metastasis) were performed at baseline (T0, before treatment), the end of the 2nd cycle (T2), and the end of the 4th cycle (T4) to assess treatment response per the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).After four treatment cycles, patients were stratified into a clinical benefit group (complete response [CR] + partial response [PR] + stable disease [SD], n=68) and a non-benefit group (progressive disease [PD], n=31) based on the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Peripheral blood samples were collected at five time points: baseline (T0), post-first cycle (T1), post-second cycle (T2), post-third cycle (T3), and post-fourth cycle (T4). Dynamic changes in neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), serum albumin (ALB), and prognostic nutritional index (PNI) were compared between groups. Line graphs and box plots were used to visualize indicator trends, while logistic regression and receiver operating characteristic (ROC) curves were applied to evaluate prognostic value. Results:Non-benefit patients showed NLR peaks at T2 and PLR peaks at T1, while benefit patients had stable levels. ALB and PNI were higher and stable in the benefit group (P<0.05). A model combining T1PLR, T1ALB, and T2NLR achieved an AUC of 0.89 (sensitivity 0.90, specificity 0.79). Conclusion:Dynamic monitoring of peripheral blood NLR, PLR, and ALB provides critical insights for predicting PD-1 immunotherapy efficacy in patients with advanced malignant melanoma. These indicators hold promise as potential clinical biomarkers to guide the development of individualized treatment strategies.

369 Background: There is an unmet need to improve the efficacy of first-line treatment in advanced GC/GEJC pts with negative or low PD-L1 expression. This Ib/II, open-label study (NCT05024812) aimed to identify the efficacy and safety of fruquintinib (VEGFR-1, -2, -3 inhibitor) plus toripalimab (anti-PD-1), and SOX as first-line therapy in GC/GEJC. Here we update the survival results and a specific focus on PD-L1 CPS features. Methods: The study of phase Ib employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) po, d1-14 , in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m2, iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. It had been reported in phase Ib that fruquintinib 5mg/d was defined as the RP2D. In phase II, a further 64 pts would be treated with the same regimen. Primary endpoint of phase II was PFS per RECIST 1.1. Secondary endpoints included ORR, DCR, OS, DOR and safety. Results: The data cut-off date was April 2025, 44 pts (9 in phase Ib; 35 in phase II) were enrolled. 43 pts had PD-L1 CPS available. 40.9% were CPS＜1 and 72.7% were CPS＜5. Of the 43 pts evaluable for tumor response, the ORR was 58.1% with 3 pts achieving complete responses and DCR was 95.3%. After a median follow-up of 12.09 months, the mPFS was 10.25 (95% CI: 5.91–NA) months and the mOS was still immature. The estimated 12-month and 18-month OS rate were 64% and 42%, respectively. Pts with CPS ＜1 were more likely to achieve higher response rate (76.5 vs 44.0%) and higher 9-month PFS rate than CPS ≥1 (81 vs 46%). Most TRAEs were grade 1-2 and grade ≥3 TRAEs occurred in 38.6% of pts. The most frequent grade 3 to 4 TRAEs were neutrophil count decreased (6.8%) and impaired liver function (6.8%). Conclusions: Fruquintinib combined with SOX and toripalimab provided promising efficacy and manageable toxicity profile as first-line therapy for pts with advanced metastatic GC/GEJC, especially in pts with negative PD-L1 expression. More data including the potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT05024812 .

Background:Early tumor shrinkage (ETS) is a superior parameter for assessing treatment responses. Our study hypothesized that an ETS with an optimal cut-off value was an imaging biomarker for advanced esophageal squamous cell carcinoma (ESCC) treated with first-line immunotherapy. Methods:We retrospectively enrolled 129 patients with unresectable locally advanced ESCC treated with first-line immunotherapy between 2019 and 2021. ETS was defined as the relative change in the longest diameters at the first evaluation compared with that at baseline. Multivariate analyses were conducted to identify the significant prognostic variables in progression-free survival (PFS) and overall survival (OS). Results:The median value of ETS was 29.5%. An ETS with a 10% cut-off value was statistically significantly associated with PFS in the univariate analysis [hazard ratio (HR): 2.26; 95% confidence interval (CI): 1.21-4.24; P=0.009]. Besides, in the univariate analysis, the longest diameter, maximum invasive depth, central necrosis on enhanced computed tomography, enhanced pattern, and ETS values were statistically significant predictive factors for OS. In the multivariate analysis, the maximum invasive depth and ETS with a 10% cut-off value were independently predictive factors for OS (HR: 0.22; 95% CI: 0.09-0.52; P=0.001, HR: 2.93; 95% CI: 1.41-6.06; P=0.004). Conclusions:ETS is associated with survival outcomes in patients with advanced ESCC treated with immunotherapy. Early tumor size shrinkage of at least 10% can be regarded as a promising biomarker predictor for PFS and OS. ETS supports clinical decisions by identifying patients who can benefit from immunotherapy.

e16005 Background: The poor prognosis of advanced esophageal cancer is worrisome, and the current first-line regimen with an effective rate is about 30%. Additionally, there is no standard second-line treatment after failure of first-line therapy. Programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) immune checkpoint inhibitors have achieved objective response rate (ORR) of 17-40%, following median overall survival (mOS) of 10.8 months in prior phase I-II clinical studies, but a large proportion of patients (pts) still failed to this response. And for CPS (combined positive score, CPS) < 1 pts, yet not have excellent treatment options. Previous study showed that nimotuzumab in combination with cisplatin and fluorouracil (PF) regimen reaching ORR of about 50%. So, we conducted the study. The primary endpoints were ORR, and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the ORR of standard treatment is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha = 0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached response. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase II study, a total of 46 pts (full analysis set, FAS) were administered. The mean age was 65 years (range, 42-77). The ORR result was 32.6% (95%CI, 19.5%-48.0%, Clopper-Pearson method). The mOS was 12.68 months with median follow-up 19.88 months. The 9-month and 12-month survival rates were 73% and 58%, respectively. Median PFS was 9.40 months. The DCR was 83%(38/46), median DoR and TTR were not reached in FAS. For those pts without first-line immunotherapy, the ORR was 29.6% and the mOS was 10.94 months, and for first-line immunotherapy, the ORR was 36.8% and the mOS was 15.0 months. The CPS < 1 stratification factor result, ORR was 37.5%(3/8), and mOS was 14.3 months. In terms of safety, the incidence of treatment emergent adverse events (TEAEs) was 61% (28/46), of which 33% (15/46) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 9% (4/46), of which 0 case related to nimotuzumab and 4 case related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma can improve ORR and prolong OS of pts with controllable toxicity.

No combined antiangiogenic and PD-1/PD-L1 blockade therapy has been investigated as a chemo-free first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). This study evaluates the efficacy and safety of anlotinib combined with benmelstobart as a chemo-free treatment in previously untreated advanced ESCC, and identifies potential predictive biomarkers using next-generation sequencing (NGS). ALTER-E-003, a single-arm, open-label phase II trial, enrolled patients with advanced ESCC across five Chinese centers. Patients received oral anlotinib 12 mg daily on days 1–14 per three-week cycle, with benmelstobart 1200 mg infused on day 1 of each cycle for up to 24 months. Thereafter, patients received anlotinib maintenance therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. NGS and fluorescent multiplex immunohistochemistry (mIHC) were performed on tumor specimens. Of 53 screened patients, 46 completed the study. The confirmed ORR was 56.5

335 Background: Immune checkpoint inhibitors (ICIs) plus chemotherapy has become the standard first-line regimen for advanced GC/GEJC, but the efficacy still needs to be improved. Fruquintinib is an oral, highly selective VEGFR 1/2/3 inhibitor that has synergistic antitumor effects when combined with ICIs/chemotherapy. Additionally, the phase III study (NCT03223376) of fruquintinib combined with paclitaxel in second-line GC/GEJC has achieved positive topline result. Therefore, this study was aimed to evaluate the efficacy and safety of fruquintinib combined with SOX and toripalimab as a first-line therapy in GC/GEJC. Methods: In this phase Ib/II, open-label trial (NCT05024812), patients (pts) aged 18-75 years who were HER2-negative with no previous anti-tumor therapy were enrolled. The Ib phase employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d, po, d1-14 (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m2, iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. The primary objective of phase Ib was to determine the DLT in first treatment cycle defining the PR2D. Additional 64 pts were enrolled in the phase II dose expansion stage using RP2D. Primary endpoint of phase II was PFS per RECIST 1.1. Secondary endpoints included ORR, DCR, OS, DOR and safety. Results: At data cut-off (August 31, 2023), 17 pts (9 in phase Ib; 8 in phase II) with median age 65 years old had been enrolled. 59% were male, 100% had ECOG PS 1 and 35% had liver metastasis. 10/17 (59%) pts were PD-L1 CPS ≥1. No DLTs were observed at all three dose levels. Fruquintinib 5mg/d was defined as the RP2D. Of the 16 pts evaluable for tumor response, 9 pts achieved PR, 7 pts achieved SD. The ORR was 56.3% (9/16), the DCR was 100% (16/16). Pts with PD-L1 CPS ＜1 were more likely to achieve better responses (4PR in 6 pts, ORR-66.7%). After a median follow-up of 5.4 months, the median PFS was 9.3 (95% CI: 4.76–NA) months and OS result was not mature. Median DOR was not reached and two responders were estimated to have a response duration ≥8.0 months. Majority of TRAEs were grade 1-2, including neutrophil count decreased (64.3%), white blood cell decreased, hypoproteinemia and platelet count decreased (all were 42.9%). Grade 3 TRAEs included neutrophil count decreased (11.8%), platelet count decreased, impaired liver function, rash, pruritus and mucositis (5.9%, one patient for each). There were no treatment related deaths in the trial. Conclusions: Fruquintinib combined with SOX and toripalimab was well tolerated, with encouraging antitumor activity as first-line treatment for advanced metastatic GC/GEJC, especially in pts with CPS ＜1. The trial is still recruiting, more data including the potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT05024812 .

e16087 Background: Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of PD-1 inhibitors combined with angiogenesis inhibitors in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab (PD-1 inhibitor) plus chemotherapy or apatinib (angiogenesis inhibitor) as neoadjuvant therapy for locally advanced ESCC. Methods: This was an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0-3M0 ESCC. Eligible patients were 18-75 years old, had ECOG PS score of 0-1. Patients received 2 cycles (1 cycle per 4 weeks) of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Feb 2022 and Dec 2023, 24 patients (19 males and 5 females) with a median age of 67 years were enrolled in the study. Twenty-one patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 95%. Nineteen patients completed surgery and all patients (100%) reached R0 resection, 3 patients (3/19, 10.5%) reached pCR, 8 patients (8/19, 42.1%) reached MPR, and 13 patients (13/19, 68.4%) had TNM downstaging. The median follow-up was 11.9 months, and the median DFS had not yet reached. Any grade and grade ≥3 adverse events occurred in 87.5% and 8.3% of 24 patients, respectively. The most common AEs were increased alanine aminotransferase (8/24, 33.3%), increased alanine aminotransferase (7/24, 29.2%) and thrombocytopenia(7/24, 29.2%). No new safety signals or treatment-related deaths were observed. Conclusions: Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03917966 .

364 Background: The optimal therapies for patients with advanced esophageal squamous cell carcinoma (ESCC) who have progressed after immune checkpoint inhibitors (ICIs) are unclear. This phase II single-arm study aimed to assess the efficacy and safety of re-challenge with camrelizumab plus apatinib in this population. Methods: This study enrolled patients with unresectable locally advanced, locally recurrent, or metastatic ESCC who had experienced prior progression on ICI treatment. Enrolled patients received camrelizumab 200 mg intravenously every two weeks along with daily oral apatinib 250 mg. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal of consent. The primary endpoint was the confirmed objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DOR), time to response (TOR), progression-free survival (PFS), overall survival (OS), 3- and 6-month PFS rates, 6-, 9- and 12-month OS rates, and safety. Results: From September 1, 2021, to March 29, 2023, 49 eligible patients were enrolled and given treatment. Among 38 treated patients who had at least one post-baseline efficacy measurement, the ORR and confirmed ORR were 36.8% (95% CI 21.8–54.0) and 13.2% (95% CI 4.4–28.1); the DCR was 89.5% (95% CI 75.2–97.1); the median DOR was 3.0 months; and the median TOR was 2.2 months. Among the 49 treated patients, the median PFS was 4.6 months (95% CI 3.8–6.5) and OS was 7.5 months (95% CI 5.5–13.6). Patients who were both PD-L1 positive and had responded to previous ICI therapy had the longest median PFS (5.7 months, 95% CI 3.9–not reached) and OS (9.6 months, 95% CI 7.5–not reached). Grade ≥ 3 treatment-related adverse events occurred in 34.7% of patients (17/49). Conclusions: This study showed promising efficacy and an acceptable safety profile of camrelizumab plus apatinib for patients with advanced ESCC who had progressed after ICI therapy. The subset of patients who were both PD-L1 positive and had a prior ICI response seemed to benefit most. Clinical trial information: NCT03736863 .

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.

BACKGROUND:With the increasing use of immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC), there remains an unmet need for options to address disease progression after prior ICIs. This single-arm phase II study evaluated the efficacy and safety of re-challenge with camrelizumab plus apatinib in patients with advanced ESCC who were previously treated with ICIs. METHODS:This study enrolled patients aged 18-75 years with unresectable locally advanced, locally recurrent, or distant metastatic ESCC who received prior ICIs. Patients received intravenous camrelizumab 200 mg every 2 weeks and oral apatinib 250 mg daily until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was the investigator-assessed confirmed objective response rate (ORR). RESULTS:Between September 1, 2021 and March 29, 2023, 49 eligible patients were enrolled and received treatment. Among the 49 patients, the confirmed ORR was 10.2 % (95 % CI 3.4-22.2), the disease control rate (DCR) was 69.4 % (54.6-81.7), the median progression-free survival (PFS) was 4.6 months (95 % CI 3.8-6.5) and overall survival (OS) was 7.5 months (5.5-13.6). Grade ≥ 3 treatment-related adverse events occurred in 17 patients (34.7 %). No treatment-related deaths occurred. CONCLUSIONS:This study showed that the confirmed ORR was modest and did not reach clinically meaningful improvement for patients with ESCC who were previously treated with ICIs, with a manageable safety profile.

Background: Neoadjuvant therapy combining camrelizumab with chemotherapy has emerged as a promising approach for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal strategy for integrating immunotherapy with chemotherapy remains to be fully defined. This single-arm phase II study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab induction followed by camrelizumab plus chemotherapy in locally advanced ESCC. Methods: Patients with clinical stage cT2-4N0M0 or cTxN1-3M0 ESCC were enrolled in the study. Patients received one dose of camrelizumab (200 mg) followed by docetaxel (75 mg/m(2)) and nedaplatin (75 mg/m(2)) plus camrelizumab (200 mg) every 3 weeks for two cycles, and then underwent surgery within 3-4 weeks. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, downstaging rate, disease-free survival (DFS), overall survival (OS), and safety. Results: In total, 55 patients were enrolled in the study between 16 April 2020 and 30 October 2021. Of these 55 patients, 53 (96.4%) completed neoadjuvant therapy, and 48 (87.3%) underwent surgery. The MPR rate was 77.1% [37/48, 95% confidence interval (CI): 62.7-88.0%]. The pCR ( ypT0N0) rate was 39.6% (19/48, 95% CI: 25.8-54.7%). All the patients had R0 resections. Primary tumor downstaging occurred in 44 (91.7%) patients, and nodal downstaging occurred in 19 (39.6%) patients. The 2-year DFS rate was 68.9% (95% CI: 53.0-80.4%), and the 2-year OS rate was 74.7% (95% CI: 60.2-84.6%). Grade >= 3 treatment-related adverse events (TRAEs) were observed in 7 (12.7%) patients. Conclusions: In conclusion, neoadjuvant camrelizumab followed by camrelizumab plus chemotherapy showed promising efficacy in treating locally advanced ESCC and had a manageable safety profile.

p53 mutations are prevalent in human cancers; approximately half of patients with esophageal cancer present these mutations. Mutant p53 (mutp53) exerts oncogenic functions that promote malignant tumor progression, invasion, metastasis, and drug resistance, resulting in poor prognosis. Some small molecules have been shown to mitigate the oncogenic function of mutp53 by restoring its wild-type activity. Although these molecules have been evaluated in clinical trials, none have been successfully used in the clinic. Here, we investigated the antitumor effects of phenethyl isothiocyanate (PEITC) in p53-mutant esophageal squamous cell carcinoma (ESCC) and elucidated its mechanism to identify new therapeutic strategies. We observed that p53R248Q is a DNA contact mutation and a structural mutation and that PEITC can restore the activity of p53R248Qin vitro and in vivo, further clarifying the antitumor activity of PEITC in cancers with different types of p53 mutations. PEITC can inhibit ESCC growth, induce apoptosis, and arrest cell cycle progression and has a preferential selectivity for ESCC with p53 mutations. Mechanistic studies showed that PEITC induced apoptosis and arrested cells at G2/M transition in cells expressing the p53R248Q mutant by restoring the wild-type conformation and transactivation function of p53; these effects were concentration dependent. Furthermore, PEITC inhibited the growth of subcutaneous xenografts in vivo and restored p53 mutant activity in xenografts. According to these findings, PEITC has antitumor effects, with its ability to restore p53R248Q activity being a key molecular event responsible for these effects.

Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.

384 Background: CAP 02 study (NCT03736863) is a single-arm phase 2 study to evaluate the efficacy and safety of camrelizumab plus apatinib (a VEGFR2 inhibitor) as second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). Cohort 1 has been published recently, which enrolled patients who progressed after or were intolerant to first-line chemotherapy. The results showed an encouraging median overall survival (OS) of 15.8 months. Here, we reported the preliminary results of cohort 2. Methods: Cohort 2 enrolled unresectable locally advanced, locally recurrent, or metastatic ESCC patients aged 18-75 years with ECOG performance status of 0-1 who had progression on or were intolerant to first-line immunochemotherapy. The disease should be controlled without progression for at least three months during the first-line treatment. Patients received camrelizumab (200 mg Q2W) and apatinib (250 mg QD) until disease progression, intolerable toxicity, or withdrawal for other reasons. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate, progression-free survival (PFS), duration of response, time to response, OS, 3/6-month PFS rates, 6/9/12-month OS rates, and safety. Results: At the data cutoff (Sep 21, 2022), 33 of the planned 40 patients with an average of 68 years old had been enrolled, including 24 (73%) males and 24 (73%) patients with an ECOG PS score of 1. Twenty-one patients (64%) were previously treated with camrelizumab combined chemotherapy and 12 with other immunochemotherapy. Among the 17 evaluable patients, seven had the best overall response of partial response and nine with stable disease; the ORR was 41%. A total of 22 patients (67%) had treatment-related adverse events (TRAEs), with 12 patients (36%) with grade≥3. The most common TRAEs included white blood cell count decreased (11 patients, 33%), hypokalaemia (9, 27%), and alanine aminotransferase increased (8, 24%). Conclusions: Current results suggested the preliminary efficacy of second-line camrelizumab plus apatinib in patients with immunochemotherapy-treated advanced ESCC, with an acceptable safety profile. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03736863 .

Abstract Background Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of camrelizumab (PD-1 inhibitor) combined with apatinib (angiogenesis inhibitor) in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab plus chemotherapy or apatinib as neoadjuvant therapy for locally advanced ESCC. Here, we reported the results of cohort 2. Methods This is an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0–3 M0 ESCC. Eligible patients were 18–75 years old, had ECOG PS score of 0–1. Cohort 2 planned to enroll patients with 4 cycles of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4–6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival, overall survival, and safety. Results Between Feb 2022 and May 2023, 21 patients were enrolled in cohort 2. 14 patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 100%. 14 patients completed surgery and all patients (100%) reached R0 resection, 4 patients (4/14, 28.6%) reached MPR, 2 patients (2/14, 14.3%) reaching pCR, and 9 patients (9/14, 64.3%) had TNM downstaging. Any grade and grade ≥ 3 adverse events occurred in 84.2% and 9.5% of 21 patients, respectively. The most common AEs were thrombocytopenia (6/21, 28.6%) and increased alanine aminotransferase (6/21, 28.6%). No new safety signals or treatment-related deaths were observed. Conclusions Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future.

Abstract Background Anti-PD-1 antibody camrelizumab monotherapy is recommended for the treatment of advanced second-line ESCC. However, the long-term survival is limited, and new effective treatments are needed. Epidermal growth factor receptor (EGFR) is usually over-expressed in more than 50% of ESCC patients(pts), and is a potential target for the treatment of ESCC. Our study aimed to assess the efficacy and safety of combination with camrelizumab and nimotuzumab (EGFR inhibitor) as second-line treatment for advanced ESCC. Methods This ongoing phase II trial in four sites in China enrolled pts aged 18–75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line treatment, and ECOG PS score of 0–1. Pts received 200 mg intravenous camrelizumab (Q2W) plus 400 mg intravenous nimotuzumab (QW) in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate (ORR), overall survival (OS). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS). Results From 2/2021 to 4/2023, 28 of the planned 42 pts with an average 63 years old had been enrolled, including 18 (64%) males and 21 (75%) patients with an ECOG PS score of 1. Nine pts had previously used anti-PD-1/PD-L1 antibody. Among the 21 evaluable pts, 8 pts achieved partial response (PR), 13 pts stable disease (SD), illustrating an ORR of 38.0% and a DCR of 100%. Median PFS was not reached. 82.1% pts experienced adverse event(AE), with 21.4% being grade ≥ 3. The most frequent AE were RCCEP (57.1%), neutrophil count decreased (17.8%), white blood cell decreased (14.2%). Conclusions Camrelizumab plus nimotuzumab demonstrated encouraging clinical efficacy and acceptable safety as second-line treatment, and might be a favorable option for pts with advanced ESCC. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03766178.

目的 依据炎症-免疫-营养评分(IINS)、循环肿瘤细胞(CTCs)计数、肿瘤异常糖链蛋白(TAP)和临床病理特征构建食管癌根治术后患者预后列线图.方法 选取2013-08-05-2021-07-02郑州大学第一附属医院接受首次手术治疗的492例食管癌患者纳入本研究队列,随机选取343例患者作为训练队列,149例患者作为验证队列.采用LASSO Cox回归模型进行数据的简化和特征选择.使用基线变量构建基于单因素和多因素Cox模型的列线图.采用一致性指数(C-index)、时间受试者工作特征曲线(ROC)、时间依赖性曲线下面积(AUC)和校准曲线评价列线图的区分度和校准度,采用决策曲线分析(DCA)评价列线图的净效益.最后,通过risk plot、时间依赖性AUC、Kaplan-Meier和限制性立方样条(RCS)评价预测因子与总生存期(OS)和无进展生存期(PFS)的关系.结果 基于OS的多因素分析,建立包含CTCs(HR=2.413,95％CI:1.757～3.314,P<0.001)、IINS(HR=13.136,95％CI:8.579～20.113,P<0.001)、TAP(HR=3.509,95％CI:2.482～4.961,P<0.001)、神经侵犯(HR=1.467,95％CI:1.088～1.979,P=0.012)和脉管侵犯(HR=1.488,95％CI:1.137～1.946,P=0.004)的列线图.时间ROC、时间依赖性AUC、校准曲线和DCA显示,列线图预测的1、2、3年OS和PFS率与实际观察结果一致.Risk plot、时间依赖性AUC、RCS和Kaplan-Meier分析显示,CTCs、IINS和TAP越高,预后越差,且与生存风险呈非线性关系.结论 CTCs、IINS和TAP可作为食管癌患者的临床预后指标.此外,包括CTCs、IINS和TAP在内的列线图模型具有较好的预测价值,有助于指导食管癌患者的临床决策,调整治疗方案和随访策略.