Background
Drugs | Approval | SC | NSCLC | SCLC | RCC | HL | HNC | UC | CRC | HCC | ESC | MPM | GC | GEJC | TNBC | BC | CC | EC |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Nivolumab | 2014-US 2015-EU 2018-PRC | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | – | – | – | – |
Pembrolizumab | 2014-US 2015-EU 2018-PRC | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | – | √ | √ | √ | √ | √ | √ |
Cemiplimab | 2018-US 2019-EU | √ | √ | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – |
Toripalimab | 2018-PRC | √ | – | – | – | – | √ | √ | – | – | – | – | – | – | – | – | – | – |
Sintilimab | 2018-PRC | – | √ | – | – | √ | – | – | – | √ | – | – | – | – | – | – | – | – |
Camrelizumab | 2019-PRC | – | √ | – | – | √ | √ | – | – | √ | √ | – | – | – | – | – | – | – |
Tislelizumab | 2019-PRC | – | √ | – | – | √ | – | √ | – | – | – | – | – | – | – | – | – | – |
Zimberelimab | 2021-PRC | – | – | – | – | √ | – | – | – | – | – | – | – | – | – | – | – | – |
Prolgolimab | 2020-RU | √ | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – |
Dostarlimab | 2021-US 2021-EU | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | √ |
Atezolizumab | 2016-US 2017-EU 2020-PRC | √ | √ | √ | – | – | – | √ | – | √ | – | – | – | – | √ | – | – | – |
Durvalumab | 2017-US 2018-EU 2019-PRC | – | √ | √ | – | – | – | – | – | – | – | – | – | – | – | √ | – | – |
Avelumab | 2017-US 2017-EU | √ | – | – | √ | – | – | √ | – | – | – | – | – | – | – | – | – | – |
Conventional chemotherapy combined with α-PD-1/PD-L1
Chemotherapy modifying the TME
Chemotherapy combined with α-PD-1
Clinical trial | Phase | α-PD-1/PD-L1 | Chemotherapy | Cancer type | Primary outcome measures |
---|---|---|---|---|---|
NCT02039674 | 1/2 | Pembrolizumab | Pemetrexed and carboplatin | Non-squamous NSCLC | ORR |
NCT02775435 | 3 | Pembrolizumab | Paclitaxel/nab-paclitaxel and carboplatin | Squamous NSCLC | PFS, OS |
NCT02819518 | 3 | Pembrolizumab | Paclitaxel; nab-paclitaxel; gemcitabine and carboplatin | TNBC | PFS, OS |
NCT03189719 | 3 | Pembrolizumab | Cisplatin and 5-fluorouracil | Esophageal or GEJ cancer | PFS, OS |
NCT03615326 | 3 | Pembrolizumab | Trastuzumab plus either 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin | HER2+ gastric or GEJ adenocarcinoma | PFS, OS |
NCT02872116 | 3 | Nivolumab | 5-fluorouracil and leucovorin plus oxaliplatin; capecitabine and oxaliplatin | Gastric cancer, esophageal or GEJ adenocarcinoma | PFS, OS |
NCT03607539 | 3 | Sintilimab | Pemetrexed and platinum | Non-squamous NSCLC | PFS |
NCT03629925 | 3 | Sintilimab | Gemcitabine and platinum | Squamous NSCLC | PFS |
NCT03134872 | 3 | Camrelizumab | Carboplatin and pemetrexed | Non-squamous NSCLC | PFS |
NCT03707509 | 3 | Camrelizumab | Gemcitabine and cisplatin | Nasopharyngeal carcinoma | PFS |
NCT03594747 | 3 | Tislelizumab | Paclitaxel/nab-paclitaxel and carboplatin | Squamous NSCLC | PFS |
NCT03663205 | 3 | Tislelizumab | Platinum and pemetrexed | Non-squamous NSCLC | PFS |
NCT02366143 | 3 | Atezolizumab | Bevacizumab plus paclitaxel and carboplatin | Non-squamous NSCLC | PFS, OS |
NCT02763579 | 3 | Atezolizumab | Carboplatin and etoposide | SCLC | PFS, OS |
NCT02425891 | 3 | Atezolizumab | Nab-paclitaxel | TNBC | PFS, OS |
NCT02367781 | 3 | Atezolizumab | Carboplatin and nab-paclitaxel | Non-squamous NSCLC | PFS, OS |
NCT03043872 | 3 | Durvalumab | Etoposide and carboplatin/ cisplatin | SCLC | OS |
Chemotherapy combined with α-PD-L1
Radiotherapy combined with α-PD-1/PD-L1
The mechanisms by which radiotherapy synergizing α-PD-1/PD-L1
Clinical studies exploring the efficacy and safety of radiotherapy combined with α-PD-1/PD-L1
Clinical trial | Phase | α-PD-1/PD-L1 | Radiotherapy | Cancer type | Primary outcome measures |
---|---|---|---|---|---|
NCT02608385 | 1 | Pembrolizumab | SBRT | Solid tumors | Recommended SBRT dose |
NCT02621398 | 1 | Pembrolizumab | Concurrent chemoradiation | NSCLC | MTD and DLT |
NCT02434081 | 2 | Nivolumab | Concurrent chemoradiation | NSCLC | Safety |
NCT02586207 | 1 | Pembrolizumab | Concurrent chemoradiation | HNSCC | Safety |
NCT02383212 | 1 | Cemiplimab | Concurrent chemoradiation | Solid tumors | Safety, DLT |
NCT02402920 | 1 | Pembrolizumab | Concurrent chemoradiation; Concurrent radiation | SCLC | DLT |
NCT02904954 | 2 | Durvalumab | SBRT | NSCLC | Pathological response rate |
NCT02125461 | 3 | Durvalumab | Concurrent chemoradiation | NSCLC | PFS, OS |
NCT02684253 | 2 | Nivolumab | SBRT | HNSCC | BOR |
NCT02952586 | 3 | Avelumab | Concurrent chemoradiation | HNSCC | PFS |
Angiogenesis inhibitor combined with α-PD-1/PD-L1
Abnormal angiogenesis hampering the antitumor immune response
Angiogenesis inhibitor synergizing with α-PD-1/PD-L1
Clinical trial | Phase | α-PD-1/PD-L1 | Angiogenesis inhibitor | Cancer type | Primary outcome measures |
---|---|---|---|---|---|
NCT02853331 | 3 | Pembrolizumab | Axitinib | RCC | PFS, OS |
NCT02501096 | 1b/2 | Pembrolizumab | Lenvatinib | Solid tumors | MTD, ORR, DLT |
NCT03517449 | 3 | Pembrolizumab | Lenvatinib | Endometrial cancer | PFS, OS |
NCT02366143 | 3 | Atezolizumab | Bevacizumab plus chemotherapy | Non-Squamous NSCLC | PFS, OS |
NCT03434379 | 3 | Atezolizumab | Bevacizumab | HCC | PFS, OS |
NCT03141177 | 3 | Nivolumab | Cabozantinib | RCC | PFS |
NCT02684006 | 3 | Avelumab | Axitinib | RCC | PFS, OS |
NCT03628521 | 1b | Sintilimab | Anlotinib | NSCLC | Safety, ORR |
NCT03794440 | 2/3 | Sintilimab | IBI305 | HCC | PFS, OS |
NCT02942329 | 1/2 | Camrelizumab | Apatinib | Gastric cancer, HCC | OS rate |
NCT03417895 | 2 | Camrelizumab | Apatinib | SCLC | Safety, ORR |
NCT03816553 | 2 | Camrelizumab | Apatinib | Cervical cancer | ORR |
NCT03394287 | 2 | Camrelizumab | Apatinib | TNBC | ORR |
NCT03359018 | 2 | Camrelizumab | Apatinib | Osteosarcoma | PFS, CBR |
NCT03086174 | 1 | Toripalimab | Axitinib | Kidney cancer, melanoma | Safety |
Dual immune checkpoint blockade or co-stimulatory molecule agonist plus α-PD-1/PD-L1
α-CTLA-4 plus α-PD-1/PD-L1
Clinical trial | Phase | α-PD-1/PD-L1 | Other immune checkpoint inhibitors (Target) | Cancer type | Primary outcome measures |
---|---|---|---|---|---|
NCT01844505 | 3 | Nivolumab | Ipilimumab (CTLA-4) | Melanoma | PFS, OS, PFS rate, OS rate |
NCT01927419 | 2 | Nivolumab | Ipilimumab (CTLA-4) | Melanoma | ORR |
NCT02060188 | 2 | Nivolumab | Ipilimumab (CTLA-4) | Colorectal cancer | ORR |
NCT02231749 | 3 | Nivolumab | Ipilimumab (CTLA-4) | RCC | ORR, PFS, OS |
NCT02477826 | 3 | Nivolumab | Ipilimumab (CTLA-4) | NSCLC | PFS, OS |
NCT02899299 | 3 | Nivolumab | Ipilimumab (CTLA-4) | Mesothelioma | OS |
NCT03043872 | 3 | Durvalumab | Tremelimumab (CTLA-4) plus chemotherapy | SCLC | OS |
NCT02812420 | 1 | Durvalumab | Tremelimumab (CTLA-4) | Urothelial cancer | Safety |
NCT02516241 | 3 | Durvalumab | Tremelimumab (CTLA-4) | Urothelial cancer | OS |
NCT02870920 | 2 | Durvalumab | Tremelimumab (CTLA-4) | Colorectal cancer | OS |
NCT02369874 | 3 | Durvalumab | Tremelimumab (CTLA-4) | HNSCC | OS |
NCT02453282 | 3 | Durvalumab | Tremelimumab (CTLA-4) | NSCLC | OS, PFS |
NCT02352948 | 2 | Durvalumab | Tremelimumab (CTLA-4) | NSCLC | OS, PFS |
NCT02340975 | 1/2 | Durvalumab | Tremelimumab (CTLA-4) | Gastric or GEJ adenocarcinoma | Safety, ORR, PFS rate |
NCT02319044 | 2 | Durvalumab | Tremelimumab (CTLA-4) | HNSCC | ORR |
NCT03081923 | 2 | Durvalumab | Tremelimumab (CTLA-4) | Germ cell tumors | ORR |
NCT02588131 | 2 | Durvalumab | Tremelimumab (CTLA-4) | Mesothelioma | ORR |
NCT02519348 | 1/2 | Durvalumab | Tremelimumab (CTLA-4) | HCC | Safety |
NCT02558894 | 2 | Durvalumab | Tremelimumab (CTLA-4) | Pancreatic ductal adenocarcinoma | ORR |
NCT03099109 | 1 | LY3300054 | LY3321367 (TIM-3) | Solid tumor | Safety |
NCT02791334 | 1 | LY3300054 | LY3321367 (TIM-3) | Solid tumor | Safety |
NCT02608268 | 1/2 | Spartalizumab | Sabatolimab (TIM-3) | Solid tumor | Safety, ORR |
NCT03470922 | 2/3 | Nivolumab | Relatlimab (LAG-3) | Melanoma | PFS |
NCT03667716 | 1 | Nivolumab | COM701 (PVRIG) | Solid tumor | Safety |
NCT03563716 | 2 | Atezolizumab | Tiragolumab (TIGIT) | NSCLC | ORR, PFS |
NCT02179918 | 1 | Pembrolizumab | PF-05082566 (4-1BB) | Solid tumor | Safety |
NCT03502330 | 1 | Nivolumab | APX005M (CD40) | Melanoma, NSCLC, RCC | Safety |
NCT03829501 | 1/2 | Atezolizumab | KY1044 (ICOS) | Solid tumor | Safety, ORR |
NCT02740270 | 1 | Spartalizumab | GWN323 (GITR) | Solid tumor, lymphomas | Safety |
α-PD-1/PD-L1 plus other ICIs
Co-stimulatory molecule agonist plus α-PD-1/PD-L1
Targeted therapy (except for angiogenesis inhibitor) combined with α-PD-1/PD-L1
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) plus α-PD-1/PD-L1
Clinical trial | Phase | α-PD-1/PD-L1 | Targeted therapy (Target) | Cancer type | Primary outcome measures |
---|---|---|---|---|---|
NCT01454102 | 1 | Nivolumab | Erlotinib (EGFR) | NSCLC | Safety |
NCT02013219 | 1 | Atezolizumab | Erlotinib (EGFR) | NSCLC | Safety, RP2D |
NCT02143466 | 1 | Durvalumab | Osimertinib (EGFR) | NSCLC | Safety |
NCT02454933 | 3 | Durvalumab | Osimertinib (EGFR) | NSCLC | Safety |
NCT02574078 | 1/2 | Nivolumab | Crizotinib (Met/ALK/ROS) | NSCLC | Safety |
NCT02511184 | 1 | Pembrolizumab | Crizotinib (Met/ALK/ROS) | NSCLC | Safety |
NCT02013219 | 1 | Atezolizumab | Alectinib (ALK/ FLT3/RET) | NSCLC | Safety, RP2D |
NCT02584634 | 2 | Avelumab | Crizotinib (Met/ALK/ROS) | NSCLC | ORR, Safety |
NCT02660034 | 1 | Tislelizumab | Pamiparib (PARP) | Solid tumor | Safety, ORR, PFS, DOR, DCR, CBR, OS |
NCT04475939 | 3 | Pembrolizumab | Niraparib (PARP) | NSCLC | PFS, OS |
NCT02657889 | 1/2 | Pembrolizumab | Niraparib (PARP) | TNBC, Ovarian cancer | Safety, ORR |
NCT02734004 | 2 | Durvalumab | Olaparib (PARP) | Ovarian cancer | DCR, ORR, Safety |
NCT02484404 | 1/2 | Durvalumab | Olaparib (PARP) | Solid tumor | RP2D, ORR |
NCT01988896 | 1 | Atezolizumab | Cobimetinib (MEK) | Solid tumor | Safety, RP2D |
NCT02322814 | 2 | Atezolizumab | Cobimetinib (MEK) | TNBC | PFS, ORR |
NCT02788279 | 3 | Atezolizumab | Cobimetinib (MEK) | Colorectal cancer | OS |
NCT03600883 | 1/2 | Unspecified | AMG 510 (KRAS) | KRAS p.G12C mutant solid tumor | Safety |
NCT02972034 | 1 | Pembrolizumab | MK-8353 (ERK) | Solid tumor | Safety |
NCT02967692 | 3 | PDR001 | Dabrafenib (RAF) and Trametinib (MEK) | Melanoma | Safety, PFS |
NCT04017650 | 1/2 | Nivolumab | Encorafenib (RAF) and Cetuximab (EGFR) | Colorectal cancer | Best radiographic response; Safety |
NCT03502733 | 1 | Nivolumab | Copanlisib (PI3K) | Solid tumor and lymphoma | Safety |
NCT03395899 | 2 | Atezolizumab | Ipatasertib (AKT) | Breast cancer | 2-fold increase in GzmB+CD8+ T cell |
NCT02393248 | 1/2 | Pembrolizumab | Pemigatinib (FGFR) | Solid tumor | Maximum tolerated dose, Pharmacodynamics |
NCT03123055 | 1/2 | Pembrolizumab | B-701 (FGFR) | Urothelial cell carcinoma | Safety, ORR |
NCT02819596 | 2 | Durvalumab | Savolitinib (c-MET) | Renal cell carcinoma | Safety, ORR |
NCT02779751 | 1 | Pembrolizumab | Abemaciclib (CDK4/6) | NSCLC, Breast cancer | Safety |
NCT04000529 | 1 | Spartalizumab | TNO155 (SHP-2) | Solid tumor | Safety |
Anaplastic lymphoma kinase (ALK)-TKI plus α-PD-1/PD-L1
RAS-targeted therapy plus α-PD-1/PD-L1
Poly (ADP-ribose) polymerase (PARP) inhibitor plus α-PD-1/PD-L1
α-PD-1/PD-L1 plus other novel targeted therapies
STING agonist plus α-PD-1/PD-L1
STING pathway and STING agonist
STING agonist plus α-PD-1/PD-L1
Bispecific/bifunctional antibody targeting PD-1/PD-L1
Target | Antibody Product | Company/Authors | Reference |
---|---|---|---|
TGF-β × PD-L1 | M7824 | Merck KGaA | [278] |
YM101 | Wuhan YZY Biopharma | [279] | |
SHR-1701 | Hengrui Pharmaceuticals | [280] | |
CTLA-4 × PD-L1 | KN046 | Alphamab Oncology | [281] |
CTLA-4 × PD-1 | MGD019 | MacroGenics | [282] |
MEDI5752 | AstraZeneca | [283] | |
LAG-3 × PD-L1 | IBI323 | Innovent Biologics | [284] |
LAG-3 × PD-1 | Tebotelimab | MacroGenics | [285] |
TIM-3 × PD-L1 | LY3415244 | Eli Lilly | [286] |
TIGIT×PD-L1 | Not given | Novamab Biopharmaceuticals | [287] |
4-1BB × PD-L1 | MCLA-145 | Merus and Incyte | [288] |
ABL503 | ABL Bio | [289] | |
PM1003 | Biotheus | [290] | |
CD27 × PD-L1 | CDX-527 | Celldex Therapeutics | [291] |
c-Met×PD-1 | Not given | Yuan et. al | [292] |
Not given | Hou et. al | [293] | |
Not given | Wu et. al | [294] | |
Not given | Sun et. al | [295] | |
EGFR×PD-L1 | Not given | Koopmans et. al | [296] |
PD-1 × PD-L1 | LY3434172 | Eli Lilly | [297] |
CD47 × PD-L1 | IBI322 | Innovent Biologics | [298] |