Table 1.
Current Research on Anti-PD-1/PD-L1 and CTLA-4 Pathway Targeted Drugs in Gastric Cancer.
| Target | Drug | Type | Clinical Research | Reference |
|---|---|---|---|---|
| CTLA-4 inhibitor | Ipilimumab | Full humanized immunoglobulin G1 antibody | A randomized, open-label, two-arm phase II trial comparing the efficacy of sequential ipilimumab (ipi) versus best supportive care (BSC) following first-line (1L) chemotherapy in patients with unresectable, locally advanced/metastatic (A/M) gastric or gastro-esophageal junction (G/GEJ) cancer（NCT01585987） | Moehler et al 38 |
| Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer (NCT01928394) | Bang et al23,39,42,55,56 | |||
| Tremelimumab | Fully humanized anti-CTLA-4 monoclonal IgG2 antibody | Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma | Ralph et al 58 | |
| TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study | Raimondi et al 59 | |||
| PD-1 inhibitor | Pembrolizumab | Humanized immunoglobulin G4 antibody | Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial | Muro et al 19 |
| Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial | Fuchs et al 14 | |||
| Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomized, open-label, controlled, phase 3 trial | Shitara et al 21 | |||
| Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy versus Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial | Shitara et al 22 | |||
| Nivolumab | Full humanized immunoglobulin G4 antibody | Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomized, double-blind, placebo-controlled, phase 3 trial | Kang et al 25 | |
| Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4) | Boku et al 30 | |||
| CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer | Janjigian et al15,27,44 | |||
| An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) | Kawakami et al 28 | |||
| Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer | Kelly et al 29 | |||
| Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer | Nakajima et al 31 | |||
| First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomized, open-label, phase 3 trial | Janjigian et al15,27,44 | |||
| PD-L1 inhibitor | Avelumab | Full humanized immunoglobulin G1 antibody | Phase III, randomized trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300 | Bang et al23,39,42,55 |
| Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial | Doi et al 35 | |||
| Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial | Chung et al 37 | |||
| Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100 | Moehler et al 38 | |||
| Atezolizumab | FC segment-modified humanized immunoglobulin G1 antibody | Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients | Herbst et al 45 | |
| Durvalumab | FC segment-modified humanized immunoglobulin G1 antibody | Ramucirumab and durvalumab for previously treated, advanced nonsmall-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ) | Bang et al23,39,42,55 | |
| Immune checkpoint inhibitors independently developed in China | Toripalimab | Human immunoglobulin G4 (IgG4) monoclonal antibody | Safety, efficacy, and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432 | Wang et al60,128 |
| Camrelizumab | Human immunoglobulin G4 (IgG4) monoclonal antibody | Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation, and Expansion Study | Xu et al 61 | |
| Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma | Peng et al 62 | |||
| Sintilimab | Human immunoglobulin G4 (IgG4) monoclonal antibody | Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial | Jiang et al64,88,140,144 | |
| Clinical Study of Sintilimab as Second-Line or Above Therapy in Patients With Advanced or Metastatic Gastric Cancer: A Retrospective Study | Nie et al 65 |