Background
Clinical experience with anti-PD-1/anti-PDL-1 agents in lung cancer
Pretreated metastatic NSCLC
Anti-PD-1 agents
Trial name | Phase | Histology | Therapy | mOS | 1-year OS (%) | DOR | mPFS | 1-year PFS (%) | mORR (%) | Ref |
---|---|---|---|---|---|---|---|---|---|---|
CheckMate 017 | 3 | SQ | NIVO | 9.2 | 42 | NR | 3.5 | 21 | 20 | [9] |
DOC | 6 | 24 | 8.4 | 2.8 | 6 | 9 | ||||
CheckMate 057 | 3 | NONSQ | NIVO | 12.2 | 50.5 | 17.1 | NR | 18.5 | 19.2 | [10] |
DOC | 9.4 | 39 | 5.6 | NR | 8.1 | 12.4 | ||||
KEYNOTE-010 | 2/3 | ALL | PEMBRO 2 (PD-L1+) | 9.4 (14.9) | NR | NR | 3.9 | NR | NR | [12] |
PEMBRO 10 (PD-L1+) | 10.8 (17.3) | NR | NR | 4 | NR | NR | ||||
DOC | 8.6 (8.2) | NR | NR | 4 | NR | NR | ||||
POPLAR | 2 | ALL | ATEZO | 12.6 | NR | NR | 4.2 | NR | 17 | [13] |
DOC | 9.7 | NR | NR | NR | NR | NR | ||||
OAK | 3 | ALL | ATEZO | 13.8 | 55 | 16.3 | 2.8 | NR | 14 | [15] |
DOC | 9.6 | 41 | 6.2 | 4.0 | NR | 13 | ||||
KEYNOTE-021 | 1/2 | ALL | PEMBRO + IPI | 17 | NR | 14 | 6 | NR | 24 | [17] |
Anti-PD-L1 agents
Combination therapy
Treatment-naïve metastatic NSCLC
Monotherapy
Combination therapy
Completed trial name | Phase | Histology | Therapy | mORR (%) | <1% PD-L1 ORR | >1% PD-L1 ORR | >50% PD-L1 ORR | <1% PD-L1 PFS | >1% PD-L1 PFS | >50% PD-L1 PFS | Ref |
CheckMate 012 | 1 | ALL | NIVO3 | 23 | 14 | 28 | 50 | 6.6 | 3.5 | 8.4 | |
NIVO3 + IPIQ12W | 47 | 30 | 57 | 100 | 4.7 | 8.1 | 13.6 | ||||
NIVO3 + IPIQ6W | 39 | 0 | 57 | 86 | 2.4 | 10.6 | NR | ||||
Trial Name | Phase | Histology | Therapy | PFS (months) | 6-month OS (%) | ORR (%) | DOR | TrAEs (%) | 3 + TrAEs (%) | ||
KEYNOTE-024 | 3 | ≥50% PD-L1 | PEMBROQ3W | 10.3 | 80.2 | 44.8 | NR | 73.4 | 26.6 | [21] | |
PT-DC | 6.0 | 72.4 | 27.8 | 6.3months | 90.0 | 53.3 | |||||
Trial name | Phase | Histology | Therapy | PFS (months) | OS | ORR | DOR | TrAEs (%) | 3 + TrAEs (%) | ||
CheckMate 026 | 3 | ≥5% PD-L1 | NIVO3 | 4.2 | pending | pending | pending | 71 | 18 | [60] | |
PT-DC | 5.9 | pending | pending | pending | 92 | 51 |
Ongoing trial name | Phase | Histology | Therapy | Setting | Endpoints (starting with primary) | Ref |
---|---|---|---|---|---|---|
KEYNOTE-021 | 1/2 | ALL | PEMBRO + PT-DC | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [17] |
KEYNOTE-189 | 3 | ALL | PT-DC alone versus PT-DC + PEMBRO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [24] |
IMPower 130 | 3 | ALL | PT-DC + ATEZO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [26] |
IMPower 111 | 3 | SQ | Gemcitabine/PT + ATEZO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [29] |
IMPower 110 | 3 | NONSQ | Pemetrexed/PT + ATEZO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [28] |
IMPower 131 | 3 | SQ | Abraxane/PT + ATEZO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [27] |
IMPower 150 | 3 | NONSQ | PT-DC/ATEZO | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [25] |
NEPTUNE | 3 | ALL | PT-DC alone versus durvalumab + tremelimumab | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [30] |
MYSTIC | 3 | ALL | Durvalumab + tremelimumab | Advanced, treatment-naïve NSCLC | PFS, ORR, OS, DOR, safety | [31] |
PEARLS | 1b/2-3a | ALL | PEMBRO versus placebo | Adjuvant NSCLC | DFS, OS, lung cancer specific survival | [32] |
SAKK 16/14 | 2 | ALL | Durvalumab | Adjuvant NSCLC | Event-free survival at 1 and 5 years, OS, ORR, safety | [33] |
NCT02259621 | 2 | ALL | NIVO | Neoadjuvant NSCLC | Safety | [34] |
Lung-MAP | 2/3 | SQ | Biomarker-driven combination with durvalumab, nivolumab, ipilimumab, and chemotherapy or targeted therapy | Advanced, pretreated SQ NSCLC | PFS, ORR, OS, DOR, safety | [16] |
Adjuvant and neoadjuvant NSCLC
Small cell lung cancer
Trial name | Phase | Therapy | mOS | 1-year OS | DOR | mPFS | 1-year PFS | mORR (%) | Ref |
NCT01450761 | 3 | Ipilimumab | 11 | NR | NR | 4.6 | NR | NR | [61] |
PT-DC | 10.9 | NR | NR | 4.4 | NR | NR | |||
CheckMate 032 | 1/2 | NIVO3 | NR | NR | NR | NR | NR | 10 | [37] |
NIVO1 + IPI1 | NR | NR | NR | NR | NR | 33 | |||
NIVO1 + IPI3 | NR | NR | NR | NR | NR | 23 | |||
NIVO3 + IPI1 | NR | NR | NR | NR | NR | 19 | |||
Ongoing trial name | Phase | Therapy | Setting | Endpoints (starting with primary) | |||||
CheckMate 331 | 3 | NIVO | Advanced SCLC | OS, PFS, ORR | [36] | ||||
CheckMate 451 | 3 | NIVO versus NIVO + IPI | Advanced SCLC | OS, PFS | [38] | ||||
KEYNOTE-028 | 1b | PEMBROQ2W | Advanced SCLC | ORR, PFS, OS, DOR | [39] | ||||
IMpower 133 | 3 | PT-DC +/-ATEZO | Advanced SCLC | OS, PFS, DOR, safety | [62] |
Malignant mesothelioma
Trial name | Phase | Therapy | mOS | 1-year OS | DOR | mPFS (weeks) | 1-year PFS | mORR (%) | Ref |
DETERMINE | 2b | Tremelimumab | 7.7 | NR | NR | NR | NR | NR | [42] |
Placebo | 7.3 | NR | NR | NR | NR | NR | |||
JAVELIN | 1 | Avelumab PD-L1+ | NR | NR | NR | 17.1 | NR | 14.3 | [43] |
Avelumab PD-L1- | NR | NR | NR | 7.4 | NR | 8.0 | |||
Ongoing trial name | Phase | Therapy | Setting | Endpoints (starting with primary) | |||||
NIBIT-MESO-1 | 2 | Durvalumab + tremelimumab | Unresectable malignant mesothelioma | ORR, DCR, PFS, OS (by PD-L1%), and safety. | [44] |