Clinical trials

Immunotherapy has established the new standard for first-line treatment of advanced or metastatic gastric cancer. However, current second-line options-predominantly consisting of targeted therapy plus chemotherapy or chemotherapy alone-confer only modest clinical benefit. Notably, pivotal phase III second-line trials (REGARD, RAINBOW, RAINBOW-Asia, FRUTIGA) exclusively enrolled patients who progressed on chemotherapy regimens; thus, high-quality evidence guiding second-line treatment specifically for immunotherapy-refractory patients remains scarce, representing a significant unmet medical need. Anti-angiogenic agents have demonstrated capacity to ameliorate the hypoxic, immunosuppressive tumor microenvironment while exerting synergistic anti-tumor effects when combined with immune checkpoint inhibitors. Exploratory studies evaluating immunotherapy combined with anti-angiogenic therapy plus chemotherapy in advanced gastric cancer patients after first-line failure have yielded encouraging efficacy signals (NCT03966118, NCT04982276), with objective response rates of 30-40% and median progression-free survival approaching 6 months. Based on this, the investigators aim to evaluate the efficacy and safety profile of fruquintinib combined with nab-paclitaxel and Iparomlimab and Tuvonralimab Injection (a novel bispecific antibody) as second-line treatment for patients with advanced gastric cancer who have experienced disease progression during or after first-line immunotherapy-containing regimens.

Purpose of the study Phase I study: to explore the optimal dose combination of irinotecan liposome + oxaliplatin + bevacizumab regimen, irinotecan liposome + oxaliplatin Phase II study: to evaluate the safety and efficacy of the second-line treatment regimen of irinotecan liposome combined with oxaliplatin and bevacizumab compared to the second-line treatment regimen of irinotecan liposome combined with 5-FU/LV in advanced pancreatic cancer Sample size 138 cases Phase I Crawl, sample size 9-18 cases. Phase II randomized controlled clinical study, historical data NAPOLI-1 study, ORR of 8.8% for irinotecan liposome + 5-FU/LV, planned trial arm ORR upgrade to 25%, calculated at 60 cases in each arm. Subject population Patients with advanced pancreatic cancer diagnosed after failure of first-line therapy, confirmed by histopathology or cytopathology, who meet the inclusion criteria and do not meet the exclusion criteria. Phase I design: Liposomal irinotecan + oxaliplatin + bevacizumab, 2-week regimen Liposomal irinotecan: start exploring with 50mg/m2 dose, preset 50mg/m2, 60mg/m2, 2 dose groups, 90min IV infusion, d1; Oxaliplatin: explored from 60mg/m2 dose, preset 60mg/m2, 85mg/m2, 2 dose groups, IV infusion, d1; Bevacizumab: 5 mg/kg, i.v., d1; Phase II study design. Trial group: Irinotecan liposomal: RP2D, i.v., 90min, d1; Oxaliplatin: RP2D, i.v., d1; Bevacizumab: 5mg/kg, i.v., d1; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months. Control: Liposomal irinotecan: 70 mg/m2 IV for 90 min, d1; Calcium folinate: 400 mg/m2, IV infusion over 30 min, d1; 5-FU: 2400 mg/m2, continuous IV infusion over 46h; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months. Notes: If the duration of irinotecan liposome infusion can be extended appropriately based on the patient\'s clinical response; if the patient withdraws from the trial due to intolerance of toxicity (e.g., neurotoxicity or myelotoxicity) induced by one of the drugs, follow up is required until PFS and OS. Translated with DeepL.com (free version)

This phase II trial studies how well gemcitabine, cisplatin and durvalumab/Pembrolizumab and surufatinib work in treating participants with advanced Biliary Tract Cancer. The international multicenter phase III clinical study TOPAZ-1 has confirmed that durvalumab combined with gemcitabine and cisplatin can bring survival benefits to advanced BTC. Whether if adding surufatinib to a standard of care can bring addition benefit needs to be explored.

The prognosis of most patients with unresectable locally advanced or metastatic colorectal cancer (CRC) remains poor despite the advancements in chemotherapy and target therapy. CAPability-01 trial investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Based on the previous findings of CAPability-01, we will further evaluate the efficacy and safety of sintilimab and chidamide in combination with fruquintinib in the same setting.