Gastric and Esophageal Cancer
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Jul 20 – Jul 27, 2026
Vactosertib plus pembrolizumab in patients with non-microsatellite instability-high metastatic colorectal or gastric cancer: a multicenter, phase Ib/IIa study.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This multicenter, open-label, single-arm phase Ib/IIa clinical trial assessed vactosertib plus pembrolizumab in 120 patients with non-MSI-high metastatic colorectal (n=108) or gastric cancer (n=12). The primary objective was to evaluate safety and tolerability, with secondary endpoints including various efficacy outcomes; the regimen demonstrated manageable safety, with treatment-related adverse events in 70.8% of patients (pruritus and rash most common). Among colorectal cancer patients, an objective response rate of 12.6% (higher in those without liver metastases: 22.5% vs. 6.3%) and a median overall survival of 13.2 months were reported; no objective responses were observed in gastric cancer patients. The study concluded vactosertib plus pembrolizumab has clinical activity in non-MSI-high mCRC, especially in patients without liver metastases.
10.1038/s41467-026-75595-4
Jul 13 – Jul 20, 2026
Perioperative tislelizumab plus chemotherapy for locally advanced gastric cancer: A randomized, prospective phase 2 trial.
CANCER CELL · Q1 JOURNAL - RANK #5/326TOP-TIER
This prospective, randomized, multicenter phase 2 trial aimed to assess the efficacy of perioperative tislelizumab plus chemotherapy for locally advanced gastric or gastroesophageal junction cancer, stratified by tumor-specific MHC class II (tsMHC-II) expression. A total of 136 operable cT3-4aN+M0 patients were randomly assigned to receive either tislelizumab plus chemotherapy or chemotherapy alone. Among tsMHC-II-positive patients, the addition of tislelizumab significantly increased the major pathological response rate (61.8% vs. 26.5%, p=0.003) and pathological complete response rate (32.4% vs. 5.9%, p=0.006). These findings highlight the potential of tsMHC-II as a predictive biomarker for perioperative immunotherapy and underscore the need for further validation.
10.1016/j.ccell.2026.06.015
A Randomized, Nivolumab-controlled, Phase 2 and Biomarker Study of Lomvastomig and Tobemstomig in Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 2 randomized, active-controlled, blinded, multicenter trial evaluated the bispecific antibodies lomvastomig and tobemstomig versus nivolumab in 190 CPI-naïve patients with advanced or metastatic squamous cell carcinoma of the esophagus. Patients were randomized 1:1:1 to lomvastomig (2100 mg Q2W, n=27, discontinued early), tobemstomig (2100 mg Q2W, n=82), or nivolumab (240 mg Q2W, n=81), with overall survival as the primary endpoint. Median OS was 4.8 months (80%CI, 2.8-5.8) for lomvastomig, 6.7 months (80%CI, 5.4-8.7) for tobemstomig, and 8.1 months (80%CI, 6.7-9.0) for nivolumab; neither bispecific antibody improved survival versus nivolumab overall. In exploratory analyses, tobemstomig showed prolonged survival in PD-L1-high (CPS≥10) and PD-L1-high/LAG3-high subgroups, suggesting PD-L1-guided treatment selection may be warranted for tobemstomig in ESCC.
10.1158/1078-0432.CCR-26-0851
Long-term outcomes and exploratory analysis from a randomized phase 3 trial of radiation dose escalation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
DRUG RESIST UPDATE · Q1 JOURNAL - RANK #2/352TOP-TIER
The goal was to examine the impact of radiation dose escalation in definitive chemoradiotherapy for unresectable ESCC. In a prospective randomized phase 3 trial, 319 patients with stage IIA-IVA ESCC received 60 Gy (n=160) or 50 Gy (n=159) of conventionally fractionated radiotherapy with concurrent chemotherapy. After a median follow-up of 99.5 months, locoregional progression-free survival at 5 and 8 years was 41.8% and 32.7% for the 60 Gy group versus 43.3% and 36.3% for the 50 Gy group (HR 1.06, 95% CI 0.80–1.39, p=0.70), without survival benefit but increased toxicity. Spatial multi-omics analyses showed immune-activated tumor microenvironments in long survivors, suggesting 50 Gy as a standard dose for these patients while identifying predictive biomarkers of resistance.
10.1016/j.drup.2026.101446
Jul 06 – Jul 13, 2026
The clinical relevance of regional lymph node microarchitecture in oesophageal cancer patients - Results from the UK MRC OE02 trial.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This study aimed to determine whether neoadjuvant chemotherapy and/or the presence of tumor alters lymph node (LN) microarchitecture and to assess associations with survival in patients from the prospective UK MRC OE02 trial. Microarchitectural features (lymphocytes, germinal centers, histiocytes) were measured in 433 LNs from 333 patients randomly assigned to neoadjuvant chemotherapy plus surgery (n=165) or surgery alone (n=168). Among patients with tumor-free nodes, germinal center density was lower in those receiving combination therapy (1% vs 2%; p=0.0004), and in the surgery-alone arm low histiocyte content correlated with improved OS (HR:0.67, 95%CI:0.46-0.97; p=0.03). These findings suggest LN microarchitecture could be an informative biomarker for immune modulation and prognosis in resectable oesophageal cancer.
10.1016/j.ejca.2026.116910
Effect of endoscopic screening for non-cardia gastric cancer: a 12-year report of a population-based randomized trial.
BMC MED · Q1 JOURNAL - RANK #19/332
This cluster randomized controlled trial in Hua County, China, enrolled 33,847 permanent residents aged 45-69 across 668 villages, comparing upper gastrointestinal endoscopic screening versus no screening for non-cardia gastric cancer (GC) over a maximum 12-year follow-up. The screening group had a non-cardia GC mortality of 13.1 per 100,000 person-years, versus 13.5 in controls. Intention-to-treat analysis revealed a 15% lower mortality (adjusted rate ratio [aRR] 0.85, 95% CI: 0.49-1.50), and per-protocol and subgroup analyses showed similar non-significant reductions (aRR 0.70 and 0.66, respectively). The principal conclusion was that endoscopic screening was associated with a non-significant reduction in non-cardia GC mortality, suggesting larger trials are necessary.
10.1186/s12916-026-05043-z
Jun 29 – Jul 06, 2026
Efficacy and safety of a novel oral anti-vasculogenic mimicry agent, CVM-1118, in advanced well-differentiated neuroendocrine tumors: a Phase IIa trial.
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This Phase IIa prospective, single-arm trial assessed foslinanib (CVM-1118), an oral anti–vasculogenic mimicry agent, in advanced well‑differentiated NETs refractory/intolerant to prior therapy. Patients (N=43; 35 efficacy‑evaluable) with grade 1–2 lung, gastrointestinal, or pancreatic NETs received CVM‑1118 200–300 mg twice daily in 28‑day cycles; primary endpoint was PFS, with ORR, DCR, OS, and safety secondary. Median PFS was 10.5 months (95% CI 5.6–22.3), ORR 3%, DCR 77%, and median OS not reached (95% CI 23.8–NR); in the full analysis set (N=43), median PFS was 8.4 months, and among those with prior everolimus, sunitinib, or PRRT (N=22), median PFS was 8.3 months. Treatment‑related AEs occurred in 44%, mostly grade 1–2, with no serious events, supporting favorable efficacy and tolerability.
10.1038/s41416-026-03515-w
Neoadjuvant Danburstotug (IMC-001) therapy in gastric, esophageal, and hepatocellular carcinoma: the NeoChance phase II study.
NPJ PRECIS ONCOL · Q1 JOURNAL - RANK #39/326
This phase II trial evaluated neoadjuvant danburstotug (20 mg/kg every 2 weeks) in resectable gastric cancer, esophageal squamous cell carcinoma, and hepatocellular carcinoma patients. Forty-eight patients received two cycles before surgery, with the primary endpoint of major pathologic response (MPR, <10% viable tumor). MPR was achieved in 2/48 patients (4.2%), failing the pre-specified endpoint, though pathologic regression ≤50% occurred in 22.9% of patients. The treatment was safe with only 6.0% grade ≥3 adverse events and no grade 4-5 events, and all patients underwent R0 resection.
10.1038/s41698-026-01571-2
Comparative safety of postoperative HIPEC with recombinant mutant TNF-α versus paclitaxel for gastric cancer peritoneal metastasis: a randomized controlled trial.
SURG ONCOL · Q1 JOURNAL - RANK #78/312
The primary objective was to compare the safety and tolerability of postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with recombinant mutant TNF-α (rmhTNF) alone, paclitaxel alone, or rmhTNF plus paclitaxel in patients with gastric cancer peritoneal metastasis. In this randomized controlled trial, 30 patients with locally advanced or metastatic gastric cancer undergoing radical surgery were assigned to one of three groups, each receiving HIPEC on postoperative days 1 and 3. There were no significant differences in postoperative recovery parameters or complication rates among groups (P>0.05), and after a 14-month median follow-up, 10 patients (34.5%) experienced recurrence. The study concluded that HIPEC with rmhTNF is safe, well tolerated, and does not hinder gastrointestinal recovery or increase complications after surgery.
10.1016/j.suronc.2026.102490
Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.
CELL REP MED · Q1 JOURNAL - RANK #15/195TOP-TIER
This study analyzed T cell dynamics in a phase II clinical trial of chemoimmunotherapy for advanced gastric cancer, using single-cell RNA and TCR sequencing of 66,813 T cells from 33 patients. Biopsies were taken pre-treatment, post-chemotherapy, and post-immunotherapy (pembrolizumab plus 5-FU/platinum). Slow progressors (prolonged progression-free survival) showed greater abundance, persistence, and recruitment of tumor-reactive T cells, increased B cell abundance, and pre-existing blood T cell clones that later appeared in tumors after immunotherapy. The study concludes these mechanisms may drive durable responses to frontline chemoimmunotherapy in advanced gastric cancer.
10.1016/j.xcrm.2026.102910
Long-term control of peritoneal metastases following claudin 18.2-targeted CAR T-Cell therapy in advanced gastric cancer.
J HEMATOL ONCOL · Q1 JOURNAL - RANK #1/98TOP-TIER
This phase I prospective clinical trial investigated the efficacy of claudin 18.2 (CLDN18.2)-targeted CAR T-cell therapy (satri-cel; NCT03874897) in three patients with advanced gastric cancer and peritoneal metastasis, all showing high CLDN18.2 expression. The methodology involved active treatment assignment and clinical monitoring for radiologic and clinical response; one patient subsequently underwent conversion surgery 8 months post-infusion, and later resection of ovarian metastases, while two others achieved overall survival of 44 and 35 months, respectively. All patients experienced durable peritoneal disease control, and ongoing CAR T-cell infiltration in tumor tissues was observed months after treatment despite peripheral blood clearance. The study concludes substantial and durable therapeutic activity of CLDN18.2 CAR T-cell therapy in this patient subset.
10.1186/s13045-026-01826-2
Jun 22 – Jun 29, 2026
A Prospective Multicenter Comparative Cohort Study of Neoadjuvant Sintilimab Plus Chemotherapy and Chemoradiotherapy in Resectable Clinical Node-Positive Esophageal Squamous Cell Carcinoma.
ANN SURG ONCOL · Q1 JOURNAL - RANK #39/312
This prospective multicenter study examined outcomes of neoadjuvant sintilimab plus chemotherapy (CIT) versus chemoradiotherapy (CRT) in 63 adults with resectable, clinical node-positive esophageal squamous cell carcinoma (ESCC). Primary and secondary endpoints included pathologic complete response (pCR), nodal downstaging, disease-free survival (DFS), and overall survival (OS). CRT achieved a higher pCR rate (52.4% vs. 31.0%, p = 0.110), with comparable nodal clearance (ypN0: 85.7% vs. 78.6%, p = 0.735) and high R0 resection rates. During a median follow-up of 22 months, DFS showed no significant differences, while OS demonstrated promising separation (p = 0.04), warranting validation in randomized trials.
10.1245/s10434-026-20024-5
First-Line Disitamab Vedotin, Tislelizumab, and S-1 in HER2-Overexpressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Arm, Phase II Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This single-arm, multicenter, phase II trial evaluated first-line disitamab vedotin (2.5 mg/kg d1), tislelizumab (200 mg d1), and S-1 (40–60 mg BID d1–14 q21d) in 57 patients with HER2-overexpressing advanced gastric/GEJ adenocarcinoma (IHC 3+ or 2±; CPS <1 54.4%). Primary endpoint was confirmed ORR by independent central review (RECIST v1.1); ORR was 89.5% (95% CI 78.5–96.0). At 28.2 months’ median follow-up, mPFS was 13.8 months (95% CI 10.3–24.0), mOS 31.9 months (95% CI 22.1–NR), and median DoR 13.3 months (95% CI 9.6–NR); CPS ≥1 vs <1 ORR 92.3% vs 87.1%, mPFS 16.7 vs 10.0 months, mOS 31.9 vs 25.4 months. Grade ≥3 treatment-related adverse events occurred in 64.9%, mainly hematologic and peripheral neuropathy; the regimen showed notable antitumor activity with manageable safety, warranting randomized validation.
10.1200/JCO-26-00277
Cell-free DNA dynamics and progression-free survival in metastatic gastroesophageal adenocarcinoma: insights from the REGIRI-PRODIGE 58 ancillary study.
NPJ PRECIS ONCOL · Q1 JOURNAL - RANK #39/326
This ancillary study analyzed cell-free DNA (cfDNA) dynamics in 34 metastatic gastroesophageal adenocarcinoma patients from the REGIRI-PRODIGE 58 trial treated with regorafenib plus irinotecan. Plasma samples were collected at multiple timepoints across two cycles, with cfDNA quantified and patients grouped by baseline and longitudinal cfDNA concentrations. Progression-free survival (PFS) was significantly longer in patients with low baseline cfDNA (4.51 vs 1.60 months, p=0.0084), and in the low-low dynamic subgroup compared to high-high (3.61 vs 1.45 months, p=0.0004). The study concludes that cfDNA concentrations are significantly associated with PFS, recommending cfDNA as a prognostic biomarker for future validation.
10.1038/s41698-026-01564-1
Efficacy and safety of infigratinib in patients with refractory advanced gastric or gastroesophageal junction adenocarcinoma harboring FGFR2 gene amplification: a single-arm, multicenter phase 2 trial.
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This single-arm, multicenter phase 2 trial evaluated the efficacy and safety of infigratinib in 21 patients with refractory advanced gastric or gastroesophageal junction adenocarcinoma harboring FGFR2 gene amplification. Patients received 125 mg of infigratinib orally once daily on a ‘3 weeks on, 1 week off’ schedule. The confirmed objective response rate was 23.8% (95% CI, 8.2-47.2), with median progression-free survival of 3.4 months and median overall survival of 6.7 months; grade 3-4 adverse events included elevated aspartate aminotransferase and neutropenia, with no treatment-related deaths. The authors concluded that the findings support continued investigation of FGFR-targeted strategies in this molecularly selected population, while emphasizing the need for larger studies and refined biomarker selection.
10.1038/s41416-026-03511-0
Jun 15 – Jun 22, 2026
A Randomized Controlled Phase 3 Trial of Oral Prednisolone Administration Versus Local Triamcinolone Injection Therapy for Esophageal Stricture Prevention After Extensive Endoscopic Submucosal Dissection (JCOG1217).
DIGEST ENDOSC · Q1 JOURNAL - RANK #17/312
A randomized controlled phase 3 trial was performed comparing oral prednisolone therapy to local triamcinolone injection for preventing esophageal stricture after extensive endoscopic submucosal dissection (ESD) in 281 patients with superficial esophageal squamous cell carcinoma across 45 institutions. Researchers measured stricture-free survival (SFS) at 12 weeks, number of endoscopic balloon dilations (EBD), dysphagia score, and adverse events (AEs). The 12-week SFS was 88.5% in the triamcinolone arm (95% CI: 81.6-92.9) and 94.8% in the prednisolone arm (95% CI: 89.4-97.5) (HR 0.672, 90% CI: 0.361-1.250; p=0.14), with Grade 3/4 AEs occurring in 8.7% and 6.7% of patients, respectively. Although both interventions achieved comparable outcomes, oral prednisolone did not prove superior for preventing esophageal stricture.
10.1111/den.70195
Adjuvant Chemoradiotherapy or Chemotherapy After D2 Gastrectomy in Gastric Cancer: A Randomized Clinical Trial.
JAMA NETW OPEN · Q1 JOURNAL - RANK #14/332
This prospective, phase 3 randomized clinical trial aimed to test whether adding radiotherapy to S-1 and oxaliplatin (SOX) improves disease-free survival in patients with T4 or node-positive gastric cancer following D2 gastrectomy. In total, 620 patients aged 18 to 70 years were enrolled at five large tertiary hospitals in China from December 2012 to August 2022, randomly assigning them (1:1) to receive either chemoradiotherapy (SOX RT) or chemotherapy alone (SOX). They measured 3-year DFS, showing no between-group difference (SOX RT vs SOX: HR, 0.98; 95% CI, 0.73-1.33), with OS also similar (HR, 0.86; 95% CI, 0.60-1.23). These findings suggest that adding radiotherapy to standard chemotherapy does not significantly improve survival outcomes, and is not recommended for routine use in this population.
10.1001/jamanetworkopen.2026.16154
Jun 08 – Jun 15, 2026
Preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis: 3-year follow-up results from JCOG1704.
GASTRIC CANCER · Q1 JOURNAL - RANK #25/147
This phase II trial (JCOG1704) aimed to evaluate the efficacy of preoperative chemotherapy using docetaxel, oxaliplatin, and S-1 (DOS) in patients with histologically confirmed HER2-negative gastric adenocarcinoma with extensive lymph node metastasis (ELM). Forty-seven patients were enrolled, receiving three cycles of preoperative DOS, followed by gastrectomy with D2 plus para-aortic lymph node dissection and postoperative S-1 treatment for one year. At the May 2025 data cutoff, the 3-year overall survival (OS) was 86.7%, progression-free survival (PFS) was 75.6%, and relapse-free survival (RFS) among R0 resected cases was 78.6%, with subgroup analysis highlighting differential outcomes based on nodal involvement. The study concludes preoperative DOS provides highly favorable survival outcomes for this patient population, suggesting its inclusion as a provisional standard of care within the JCOG community despite the absence of a subsequent phase III trial.
10.1007/s10120-026-01766-3
NRG-GI007: Phase I study of OBP-301, an oncolytic virus, and definitive chemoradiation in locally advanced esophageal cancer.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This phase I study evaluated the safety and efficacy of OBP-301, an oncolytic virus, combined with definitive chemoradiation (carboplatin/paclitaxel and 50.4 Gy RT) in 15 patients with locally advanced esophageal cancer. Patients received intra-tumoral OBP-301 injections before and during RT, with primary endpoints focusing on dose-limiting toxicity (DLT) and secondary endpoints including clinical complete response (cCR) and survival rates. No DLTs were observed, and the most common grade 3/4 toxicities were neutropenia (40%) and lymphopenia (33%). The cCR rate was 100% (95% CI: 77, 100) in restaged patients (n=13) and 87% (95% CI: 62, 96) overall, with 60% (9/15) alive and 53% (8/15) progression-free at 1 year, demonstrating feasibility and promising efficacy.
10.1016/j.ijrobp.2026.05.057
Nimotuzumab Combined With Concurrent Curative Radiotherapy and S-1 in 75 Years and Older Patients With Stage II-IVB Esophageal Squamous Cell Carcinoma: A Phase II Study.
INT J CANCER · Q1 JOURNAL - RANK #77/326
Nimotuzumab combined with concurrent radiotherapy and S-1 was evaluated in a prospective, single-center, phase II trial of 56 patients aged ≥75 years with Stage II–IVB esophageal squamous cell carcinoma. The primary endpoint was progression-free survival (PFS); secondary measures included overall survival (OS), treatment response, adverse events, nutritional indicators, and quality of life (QOL). Results showed a median PFS of 25.3 months, median OS of 28.2 months, a high response rate, and mostly grade 1–2 adverse events (85.7%). The study concluded that nimotuzumab plus concurrent therapy provides a promising treatment option by maintaining nutritional status and improving QOL for this vulnerable patient population.
10.1002/ijc.70550
Jun 01 – Jun 08, 2026
Pocket-creation versus conventional method in endoscopic submucosal dissection of gastric body tumor: a randomized controlled non-inferiority, multicenter trial.
GASTROINTEST ENDOSC · Q1 JOURNAL - RANK #15/147
This multicenter, prospective, randomized controlled non-inferiority trial compared pocket-creation method (PCM) versus conventional method (CM) for endoscopic submucosal dissection (ESD) of gastric body tumors at three South Korean centers from December 2021 to January 2024. 140 patients were randomized (70 per group) with the primary outcome being post-ESD adverse events (perforation, bleeding, electrocoagulation syndrome). The overall adverse event rate was 14.3% in PCM and 12.9% in CM, with an absolute risk difference of 1.4% (95% CI: -12.77% to 9.92%), meeting the non-inferiority margin of 15%. Secondary outcomes showed comparable en bloc (98.6% vs 98.6%) and complete resection rates (92.9% vs 88.6%), but significantly fewer subsequent surgical operations in the PCM group (2.9% vs 12.9%, p=0.028). The authors conclude PCM is non-inferior to CM regarding adverse events and is an effective, safe alternative for gastric body ESD.
10.1016/j.gie.2026.06.002
Long-Term Outcomes of Endoscopic Submucosal Dissection for Esophageal Squamous High-Grade Dysplasia and Early Squamous Cell Carcinoma in the West: Absolute vs Outside Criteria.
CLIN GASTROENTEROL H · Q1 JOURNAL - RANK #9/147TOP-TIER
This prospective single-center cohort study aimed to evaluate the long-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous high-grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) among Western patients. Investigators recruited 75 patients (mean age 72.9 ± 8.2 years; 62.7% female; median lesion size, 40 mm) over 92 months, comparing absolute vs outside Japanese criteria for ESD. They found curative resection rates of 71.8% vs 19.4%, with 5-year overall survival rates of 95.5% and 61.4% in curative vs noncurative resections, respectively, and 87.5% for those receiving adjuvant therapy. They concluded that ESD provides definitive T-staging, excellent procedural outcomes, and durable local control, especially for absolute criteria lesions, but can also offer organ preservation for outside criteria cases.
10.1016/j.cgh.2026.04.030
Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This randomized, double-blind, multicentre phase 3 trial (ASTRUM-006) evaluated perioperative serplulimab with neoadjuvant SOX chemotherapy versus perioperative SOX chemotherapy alone in 588 patients with PD-L1-positive, resectable gastric or gastro-oesophageal junction adenocarcinoma. Patients were randomly allocated to receive serplulimab or placebo with SOX for three cycles preoperatively, followed by adjuvant serplulimab or SOX. Median event-free survival was significantly prolonged with serplulimab (not reached vs 42.0 months; HR 0.65, 95% CI 0.47–0.90, p=0.0082 in CPS ≥10; not reached vs 35.9 months, HR 0.73, 95% CI 0.56–0.94, p=0.015 in ITT), with fewer grade 3 or worse adverse events. The authors concluded this regimen improves event-free survival and safety for this patient group.
10.1016/S0140-6736(26)00974-8
EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, double-blind, randomized phase 2 trial investigated whether adding the EP4 antagonist ONO-4578 to nivolumab plus oxaliplatin-based chemotherapy improves outcomes in chemotherapy-naïve patients with HER2-negative unresectable or recurrent gastric/gastroesophageal junction cancer. Two hundred twenty-six patients were randomized 2:1 to ONO-4578 (n = 150) or placebo (n = 76) combined with nivolumab and chemotherapy; the primary endpoint was investigator-assessed progression-free survival (PFS), with overall survival (OS), objective response rate (ORR) and safety as secondary endpoints. The ONO-4578 arm showed superior PFS (HR 0.67; 90% CI 0.48–0.92; p = 0.040), improved OS at interim analysis (HR 0.60; 95% CI 0.37–0.96) and higher ORR (62.0% vs 48.7%); diarrhea (55.7%) and anemia (55.0%) were common adverse events. The authors conclude that ONO-4578 plus nivolumab and chemotherapy offers promising first-line efficacy with acceptable safety, meriting phase 3 confirmation.
10.1200/JCO-26-01072
Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This open-label, multicenter phase 2 clinical trial evaluated the efficacy and safety of savolitinib, an oral MET inhibitor, in patients with MET-amplified, locally advanced or metastatic gastric or gastroesophageal junction cancer in China. A total of 110 patients were enrolled across exploratory (n=45) and pivotal (n=65) phases, receiving oral savolitinib after progressing on prior systemic therapies; the pivotal phase required MET gene copy number ≥10. The pivotal phase yielded an objective response rate (ORR) of 32.3% (95% CI: 21.2-45.1%), meeting the prespecified efficacy threshold, with grade ≥3 treatment-related adverse events in 34.5% of all participants and one (0.9%) treatment-related death. The study concludes that savolitinib displays promising antitumor activity and manageable safety in this population, meriting further randomized trials.
10.1038/s41591-026-04459-7
May 25 – Jun 01, 2026
Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma, with or without peritoneal metastases: a post-hoc analysis on RATIONALE-305 study.
ECLINICALMEDICINE · Q1 JOURNAL - RANK #11/332
This post-hoc analysis of the randomized, double-blind, phase 3 RATIONALE-305 clinical trial examined the efficacy and safety of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment in 997 patients with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), including those with and without peritoneal metastases. Patients were randomized 1:1 to receive either treatment regimen until disease progression or unacceptable toxicity, with outcomes measured as overall survival (OS), progression-free survival (PFS), and safety. Results showed tislelizumab plus chemotherapy significantly improved OS versus placebo plus chemotherapy in both patient subgroups: HR 0.78 (95% CI, 0.64-0.96) for those with peritoneal metastases and HR 0.79 (95% CI, 0.65-0.95) for those without; PFS benefits were similarly observed. The safety profile was comparable across treatment arms and subgroups.
10.1016/j.eclinm.2026.103980
Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This open-label, randomized phase 3 trial compared first-line zanidatamab plus chemotherapy with or without tislelizumab versus trastuzumab plus chemotherapy in HER2-positive advanced gastroesophageal adenocarcinoma. Patients were assigned 1:1:1; primary endpoints were progression-free survival (PFS) and overall survival (OS); median follow-up was 25.9 months. PFS was longer with zanidatamab regimens (12.4 months in both arms) than with trastuzumab (8.1 months): HR 0.63 (95% CI 0.51–0.78; P<0.001) for zanidatamab+tislelizumab and 0.65 (0.52–0.81; P<0.001) for zanidatamab. OS improved with zanidatamab+tislelizumab (26.4 vs 19.2 months; HR 0.72, 95% CI 0.57–0.90; P=0.004) but not significantly with zanidatamab alone (24.4 months; HR 0.80; P=0.06); grade ≥3 adverse events occurred in 83.3%, 73.8%, and 74.5%, with diarrhea in 24.8%, 20.0%, and 12.9%, respectively.
10.1056/NEJMoa2517729
Pathological Outcomes After Uncertain Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer.
ANN SURG · Q1 JOURNAL - RANK #10/312
This study investigated pathological outcomes in patients with esophageal cancer exhibiting uncertain tumor response after neoadjuvant chemoradiotherapy (nCRT) within the SANO trial. It included 272 patients with residual tumor suspicion at restaging 4-12 weeks after nCRT, of which 205 underwent esophagectomy: 15% (95% CI 10-20) had a complete pathological response. Non-traversable lesions were associated with the highest complete pathological response rate at 26% (95% CI 17-37), rising to 33% (95% CI 21-48) for those with squamous cell carcinoma. The study concludes that esophagectomy is recommended for most patients with uncertain tumor responses, given that 85% still had residual disease, though non-traversable lesion subgroup outcomes warrant nuanced clinical decision-making.
10.1097/SLA.0000000000007101
Sequential versus concurrent neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma: a randomized, controlled, open-label, phase 2 trial (HCHTOG1906).
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This open-label, phase II randomized controlled trial (HCHTOG1906) evaluated sequential versus concurrent neoadjuvant immunochemotherapy in 70 patients with resectable locally advanced esophageal squamous cell carcinoma. Patients were randomized 1:1 to sequential (paclitaxel/cisplatin day 1, toripalimab day 3) or concurrent (all drugs day 1) regimens. The overall pathological complete remission (pCR) rate was 22.2% (12/54), with no significant difference between groups (17.8% vs. 26.9%, P=0.636); however, the concurrent group had significantly higher nausea and diarrhea and more treatment-related deaths (5 vs. 1). There were no significant differences in overall survival (P=0.780) or disease-free survival (P=0.632), leading to the conclusion that while efficacy was similar, concurrent administration increased toxicity and fatal adverse events.
10.3389/fimmu.2026.1770662
May 18 – May 25, 2026
Autologous T Cell Antigen Coupler Targeting HER2 (TAC01-HER2) in Advanced or Metastatic Solid Tumors.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 1, first-in-human, open-label dose-escalation and dose-expansion trial evaluated TAC01-HER2, an autologous T-cell antigen-coupler therapy targeting HER2, in 23 patients with advanced or metastatic HER2-positive solid tumors. Patients received escalating doses up to the recommended phase 2 dose of 6–8 × 10⁶ cells/kg; safety (primary) and preliminary antitumor activity were assessed through adverse-event monitoring and RECIST responses. Treatment-related cytokine release syndrome occurred in 60.9 % of patients, anemia and elevated ALT in 21.7 % each; no treatment-related deaths or discontinuations occurred. Among 18 evaluable patients, disease control rate was 61.1 %, with two partial responses in nine gastric/GEJ cancer patients, median progression-free survival 2.6 months (0.8–12.4) and 6-month overall survival 57.9 % (95 % CI 36.3–76.9%), supporting safety, feasibility, and early signs of efficacy for TAC01-HER2 therapy.
10.1016/j.annonc.2026.05.696