Table 3 Ongoing trials of advanced NSCLC that may change clinical practice in 5 years

Standard medical therapy ± surgery/RT

Phase III

NCT03827577 (OMEGA)

195

OS

Chemotherapy/erlotinib/pembrolizumab ± RT

Phase II/III

NCT03137771 (NRG-LU002)

400

PFS/OS

Systemic anti-cancer therapy ± RT

Phase III

NCT02417662 (SARON)

340

OS

Standard of Care ± RT

Phase II/III

NCT02759783 (CORE)

206

PFS

osimertinib ± LCT

Phase II

NCT03410043 (NORTHSTAR)

143

PFS

Brigatinib + LCT

Phase I

NCT03707938 (BRIGHTSTAR)

35

Incidence of adverse events

ipilimumab + nivolumab ± LCT

Phase III

NCT03391869 (LONESTAR)

360

OS

KRAS inhibitor monotherapy

Sotorasib

KRAS G12C inhibitor

Phase III

NCT04303780 (CodeBreaK200)

345

PFS

Adagrasib

KRAS G12C inhibitor

Phase III

NCT04685135 (KRYSTAL-12)

340

PFS

JDQ443

KRAS G12C inhibitor

Phase Ib/II

Phase III

NCT04699188 (KontRASt-01)

NCT05132075 (KontRASt-02)

425;

360

DLT, AE, SAE, dose interruptions and reductions, dose intensity, ORR;

PFS

D-1553

KRAS G12C inhibitor

Phase I/II

NCT04585035 (D1553-101)

NCT05383898

200

203

DLT, AE, Plasma concentration;

DLT, AE, ORR

GDC-6036

KRAS G12C inhibitor

Phase Ia/b

Phase II/III

NCT04449874 (GO42144)

NCT03178552 (BFAST-cohort G)

498

1000 (all cohorts)

AE, DLT;

PFS

Combination with KRAS inhibitors

Sotorasib + RMC-4630

KRAS G12C; SHP2 inhibitor

Phase II

NCT05054725

46

ORR

Sotorasib/Adagrasib + TNO155

KRAS G12C; SHP2 inhibitor

Phase I/II

NCT04185883 (CodeBreak101)

NCT04330664 (KRYSTAL-2)

1054 (all cohorts)

86

DLT, TEAE, AE, vital signs, ECG, laboratory test values, ORR;

AE, Plasma concentration

Adagrasib + pembro

KRAS G12C; immune checkpoint inhibitor

Phase II

NCT04613596 (KRYSTAL 7)

250

ORR

Adagrasib + BI1701963

KRAS G12C; SOS1 inhibitor

Phase I/Ib

NCT04975256 (KRYSTAL 14)

100

TRAE, Plasma concentration, DLT

Selitrectinib

Next generation TRK inhibitor

Phase I/II

NCT03215511

81 (adult and pediatric patients)

MTD, recommended dose, ORR

Repotrectinib

Next generation TRK /ROS1 inhibitor

Phase I/II

NCT04094610

NCT03093116

(TRIDENT-1)

75 (adult and pediatric patients);

500 (all arms)

DLT, ORR;

DLT, RP2D, ORR

T-DXd

ADC

Phase II

Phase III

NCT04644237 (DESTINY-Lung02)

NCT05048797 (DESTINY-Lung04)

150

264

ORR

PFS

T-DM1

ADC

Phase II

NCT02675829

140

ORR

A166

ADC

Phase I/II

NCT03602079

49

MTD

Pyrotinib

TKI

Phase III

NCT04447118 (PYRAMID-1)

150

PFS

Poziotinib

TKI

Phase III

NCT05378763 (PINNACLE)

268

PFS

HER3-DXd

HER3

Phase II

Phase I

NCT04619004 (HERTHENA-Lung01)

NCT03260491

420

264

ORR;

DLT, AE, ORR, maximum serum concentration, area under the serum concentration–time curve

ABBV-399

C-MET

Phase II

Phase III

NCT03539536

NCT04928846

270

698

ORR, AE;

PFS, OS

IMMU-132

TROP-2

Phase II

Phase III

NCT03964727 (TROPICS-03)

NCT05089734

165

520

ORR;

OS

DS-1062

TROP-2

Phase III

NCT04656652 (TROPION-LUNG01)

590

PFS, OS

SAR408701

CEACAM5

Phase III

NCT04154956 (CARMEN-LC03)

554

PFS, OS

SAR408701 + ramucirumab

CEACAM5; Immune checkpoint inhibitor

Phase II

NCT04394624 (CARMEN-LC04)

36

DLT, ORR

SAR408701 + pembro

CEACAM5; Immune checkpoint inhibitor

Phase II

NCT04524689 (CARMEN-LC05)

120

DLT

Atezo + tirago

Anti-PD-L1; anti-TIGIT

Phase III

NCT04294810 (SKYSCRAPER-01)

635

PFS, OS

Pembro + MK-7684a

Anti-PD-1; anti-TIGIT

Phase III

NCT04738487 (MK-7684A-003)

1246

OS (stratified by PD-L1 expression)

Pembro + Eftilagimod alpha

Anti-PD-1; anti-LAG3

Phase II

NCT03625323 (TACTI-002)

189

ORR

Pembro + Lenvatinib + chemo

Anti-PD-1; anti-VEGF

Phase III

NCT03829319 (LEAP-006)

726

DLT, AE, PFS, OS

Pembro + Lenvatinib

Anti-PD-1; anti-VEGF

Phase III

NCT03976375 (LEAP-008)

405

OS, PFS