Table 1 Representative phase II/III RCTs with iRT in unresectable LA-NSCLC

cCRT or sCRT followed by ICIs consolidation treatment

 NCT02125461 (PACIFIC) [9, 49, 70]

III

Completed

713

Durva

CCRT > durva vs. cCRT > placebo

PFS, OS

Median 16.9 vs. 5.6

5-yr 33.1% vs.19.0%

Median 47.5 vs. 29.1

5-yr 42.9% vs.33.4%

30.5% vs. 26.1%

 NCT02343952 (LUN14-179) [52]

II

Completed

92

Pembro

CCRT > pembro

TMDD

Median 18.7

Median 35.8

4.3%

 NCT03728556 (GEMSTONE-301) [55, 56]

III

Completed

381

Suge

CCRT/sCRT > suge vs. cCRT/sCRT > placebo

PFS

Median 10.5 vs. 6.2

Median NR vs. 25.9

3-yr 55.8% vs. 29.5%

9.0% vs. 6.0%

 PACIFIC-6 (NCT03693300) [57]

II

Completed

120

Durva

SCRT > durva

Grade ≥ 3 AEs

Median 10.9

1-yr 49.6%

Median 25

1-year 84.1%

20.5%

 NCT03706690 (PACIFIC-5)

III

Ongoing

400

Durva

CCRT/sCRT > durva vs. cCRT/sCRT > placebo

PFS

-

-

-

 NCT03379441

II

Ongoing

126

Pembro

CCRT/sCRT > pembro

OS

-

-

-

 NCT03728556

III

Ongoing

381

CS1001

CCRT/sCRT > CS1001 vs. cCRT/sCRT > placebo

PFS

-

-

-

 NCT04325763

III

Ongoing

315

TQB2450

CCRT/sCRT > TQB2450 + anlotinib vs. CCRT/sCRT > TQB2450 vs. CCRT/sCRT > placebo

PFS

-

-

-

 BTCRC-LUN 16–081 (NCT03285321) [64]

II

Completed

108

Nivo/ipili

CCRT > nivo + ipili vs. cCRT > nivo

PFS

Median 25.4 vs. 25.8

Median NR

2-yr 78% vs. 81%

52.9% vs. 38.9%

 COAST (NCT03822351) [66]

II

Completed

189

Durva/olec/mona

CCRT > durva + olec vs. cCRT > durva + mona vs. cCRT > durva

ORR

Median NR vs. 15.1 vs. 6.3

1-yr 62.6% vs. 72.7% vs. 33.9%

Median NR

40.7% vs. 27.9% vs. 39.4%

 NCT04513925

(Skyscraper-03)

III

Ongoing

800

Atezo/tirago/durva

CCRT > atezo + tirago vs.cCRT > durva

PFS

-

-

-

 NCT04026412

(Checkmate 73L) [65]

III

Ongoing

888

Nivo/ipili/durva

CCRT + nivo > nivo + ipili vs. cCRT + nivo > nivo vs. cCRT > durva

PFS, OS

-

-

-

 NCT05221840 (Checkmate-9)

III

Ongoing

999

Durva/olec/ mona

CCRT > durva + olec vs. cCRT > durva + mona vs. cCRT > durva

PFS

-

-

-

 NCT04905316 (CHORUS)

II

Ongoing

32

Durva/ canaki

CCRT + canaki > canaki + durva

PFS

-

-

-

Combination of cCRT and ICIs followed by ICIs maintenance treatment

 NCT03631784 (KEYNOTE-799) [71, 72]

II

Completed

216

Pembro

CCRT + pembro > pembro

ORR

Arm A Median 30.6

1-yr 67.1%

2-yr 55.3%

Arm A Median NR

1-yr 81.3%

2-yr 64.3%

Arm A 64.3%

Grade ≥ 3 pneumonitis 8.0%

Arm B NR

1-yr 76.6%

2-yr 60.6%

Arm B Median NR

2-yr 87%

2-yr 71.2%

Arm B 50.0%

Grade ≥ 3 pneumonitis 6.9%

 NICOLAS (NCT02434081) [73, 74]

II

Completed

79

Nivo

CCRT + nivo > nivo

Grade ≥ 3 pneumonitis

1-yr 53.7%

Median 12.7

1-yr NR

Median 38.8

Grade ≥ 3 pneumonitis 11.7%

 NCT02525757 (DETERRED) [75]

II

Completed

52

Atezo

CCRT + atezo (sequential) > atezo vs. CCRT + atezo (concurrent) > atezo

Grade ≥ 3 AEs

Median 18.6 vs. 13.2

1-yr ~ 55% vs. ~ 52%

Median 22.8 vs. NR

1-yr ~ 80% vs. ~ 80%

80% vs. 80%

 NCT03519971 (PACIFIC 2)

III

Ongoing

328

Durva

CCRT + durva > durva vs. cCRT + placebo > placebo

PFS

-

-

-

 NCT03945227 (PASTURE)

II

Ongoing

200

PDR001

CRT + PDR001 > PDR001 vs. CRT > PDR001

PFS

-

-

-

 NCT04092283

III

Ongoing

660

Durva

CCRT + durva > durva vs. cCRT + placebo > durva

OS

-

-

-

 NCT04380636 (KEYLYNK-012)

III

Ongoing

870

Pembro/olaparib/durva

CCRT + pembro > pembro vs. cCRT + pembro > pembro + olaparib vs. cCRT + durva

PFS, OS

-

-

-

 NCT04085250

II

Ongoing

264

Nivo

CT + nivo > cCRT + nivo > nivo vs. CT + nivo > cCRT + nivo > FU

PFS

-

-

-

 NCT03840902

III

Ongoing

350

Durva/ M7824

CCRT + M7824 > M7824 vs

cCRT + durva

PFS

-

-

-

 NCT04765709 (BRIDGE trial)

II

Ongoing

65

Durva

CT + durva > durva + RT > durva

PFS

-

-

-

CCRT following induction ICIs followed by ICIs maintenance treatment

 NCT03102242 (AFT-16) [76]

II

Completed

64

Atezo

Atezo > CRT > atezo

DCR

Median 23.7

1-yr 66%, 18 mo 57%

Median NR

18 mo 84%

Median NR

 NCT03523702 (SPRINT) [77]

II

Ongoing

63

Pembro/ durva

Pembro > RT > pembro (PD-L1 ≥ 50%) vs. cCRT > durva (PD-L1 < 50%)

PFS

PD-L1 ≥ 50%

1-yr 73%

PD-L1 ≥ 50%

1-yr 91%

Median NR

 NCT04776447 (APOLO)

II

Ongoing

51

Atezo

Atezo + CT > cCRT > atezo

PFS

-

-

-

 NCT04364048

II

Ongoing

54

Durva

Durva > cCRT > durva

PFS

-

-

-

 NCT04230408 (PACIFIC BRAZIL)

II

Ongoing

48

Durva

Durva + CT > cCRT + durva > durva

PFS

-

-

-

 NCT05128630 (DEDALUS)

II

Ongoing

45

Durva

CT + durva > RT + durva > durva

Safety

-

-

-