Tumor type | Target | Drug | Phase and identification | Sample size | Clinical end point | TRAEs | Reference |
---|---|---|---|---|---|---|---|
GC/GEC | PD-1 | Nivolumab | Phase III NCT02267343 | 493 | ORR 11.2% (nivolumab), 0% (placebo); median PFS 1.61 months (nivolumab), 1.45 months (placebo); median OS 5.32 months (nivolumab), 4.14 months (placebo) | Grade ≥3 11.5% (nivolumab), 5.5% (placebo) | ASCO 2017 [36] |
GC/GEC | PD-1 | Nivolumab | Phase I/II NCT01928394 | 59 | ORR 12% (all), 18% (PD-L1+), 12% (PD-L1−); median DOR 7.1 months; median OS 6.8 months; 12-month OS rate 38% | All grade: 66%; grades 3–4 14%, including pneumonitis, fatigue, diarrhea, vomiting, hypothyroidism, increased aspartate and alanine aminotransferase and alkaline phosphatase levels. | ASCO 2016 [78] |
GC/GEC | PD-L1 | Avelumab | Phase I NCT01772004 | 75 | ORR 15% (2 line group), 7% (switch-maintenance group); median PFS in 2 line group 36.0 weeks (PD-L1+), 11.6 weeks (PD-L1−); median PFS in switch-maintenance group 17.6 weeks (PD-L1+), 11.6 weeks (PD-L1−) | TR-TEAEs of any grade 62.7%, including infusion-related reaction; grade ≥3 TR-TEAE 12.0%, including fatigue, thrombocytopenia, and anemia | ASCO 2016 [152] |
GC | PD-1 | Pembrolizumab | Phase II NCT02335411 | 259 | ORR 11.2% (all), 14.9% (3 line), 7.2% (4 line), 15.5% (PD-L1+), 5.5% (PD-L1−), 21.3% (3 line with PD-L1+), 6.9% (4 line with PD-L1+); SD 17%; PD 55.6%; Median DOR: 8.1 months | Grades 3–5 16.6% | ASCO 2017 [153] |
GC | PD-1 | Pembrolizumab + 5-fluorouracil + cisplatin | Phase II NCT02335411 | 25 | ORR 60% (all), 68.8% (PD-L1+), 37.5% (PD-L1−); SD 32%; PD 55.6%; median DOR 4.6 months (all), 4.6 months (PD-L1+), 5.4 months (PD-L1−); median PFS 6.6 months; median OS13.8 months | Grades 3–4 76% | ASCO 2017 [154] |
GC | PD-1 | Pembrolizumab | Phase I NCT01848834 | 36 | ORR 22% (central review), 33% (investigator review) | Any grade 67%, including fatigue, decreased appetite, hypothyroidism, pruritus and arthralgia; 5 (13%) patients had a total of 6 grades 3–4 TRAEs, including fatigue, pemphigoid, hypothyroidism, peripheral sensory neuropathy, pneumonitis. | Lancet Oncology 2016 [35] |
GC | PD-1 | Nivolumab; nivolumab + ipilimumab | Phase I/II NCT01928394 | 154 | ORR 16% (all), 14% (nivolumab 3 mg/kg), 26% (nivolumab 1 mg/kg + ipilimumab 3 mg/kg), 10% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg); DCR 38%; 12-month OS rate 36% (nivolumab 3 mg/kg), 34% (nivolumab 1 mg/kg + ipilimumab 3 mg/kg), NA (nivolumab 3 mg/kg + ipilimumab 1 mg/kg); median OS 5.0 months (nivolumab 3 mg/kg), 6.9 months (nivolumab 1 mg/kg + ipilimumab 3 mg/kg), 4.8 months (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | Any grade 70% (nivolumab 3 mg/kg), 84% (nivolumab 1 mg/kg + ipilimumab 3 mg/kg), 75% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg); grades 3–4: 17% (nivolumab 3 mg/kg), 45% (nivolumab 1 mg/kg + ipilimumab 3 mg/kg), 27% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | ASCO 2016 [155] |
GC | PD-1 | Pembrolizumab | Phase I NCT01848834 | 39 | ORR 22% (central review), 33% (investigator review); median DOR 24 weeks; 6-month PFS rate 24%; 6-month OS rate 69% | 4 patients experienced 5 total grades 3–5 TRAEs, including peripheral sensory neuropathy, fatigue, decreased appetite, hypoxia, and pneumonitis; 1 patient experienced drug-related death (hypoxia) | ASCO 2015 [156] |
GC | PD-L1 | Avelumab | Phase I NCT01943461 | 11 | PR 3 patients | All grades 90.9%, including infusion-related reactions, hyperthyroidism, and pruritus | ASCO 2015 [129] |
GC | PD-L1 | Durvalumab | Phase I NCT01693562 | 16 | ORR 25% | Any grade (multiple cancer types) 33%, including fatigue, nausea, rash, vomiting, and pyrexia; grade ≥3 (multiple cancer types) 7% | ASCO 2014 [61] |
GC | PD-L1 | Atezolizumab | Phase I NCT01375842 | 1 | PR 1patient | Grades 3–4 (multiple cancer types) 39% | ASCO 2013 [134] |