Table 2.

Summary of ongoing clinical trials investigating KRAS(G12C) inhibitors alone or in combination with other treatment modalities in NSCLC. ORR = objective response rate, PFS = progression-free survival, TRAE = treatment-related adverse events.

Drug	Trial #	Clinical Phase	Efficacy (%)	Median PFS	Reported Toxicity Any Grade in % (Grade 3–4 in %)	Data Cutoff
Sotorasib (AMG510) −/+pembrolizumab	NCT03600883 CodeBreak 100	Phase 1/2 recruiting	ORR 37.1 Complete response 2.4 Partial response 34.7 Stable disease 43.5Progressive disease 16.1 Disease control rate 80.6	6.8 months	Diarrhea 69.8 (19.8) Nausea 19.0 (0) ALT increase 15.1 (6.3) AST increase 15.1 (5.6) Fatigue 11.1 (0) Vomiting 7.9 (0) Rash 5.6 (0) Treatment discontinuation in 7.1%	1 December 2020 with a median follow-up time of 12.2 months
Sotorasib (AMG510) +MEK inhibitor or anti-PD1	NCT04185883 CodeBreak 101	Phase 1b recruiting	-	-	-	-
Sotorasib (AMG510) in subjects of Chinese descent	NCT04380753 CodeBreak 105	Phase 1 recruiting	-	-	-	-
Sotorasib (AMG510) vs. docetaxel	NCT04303780 CodeBreak 200	Phase 3 recruiting	-	-	-	-
Adagrasib (MRTX849) −/+pembrolizumab −/+afatinib	NCT03785249 KRYSTAL-1	Phase 1/2 recruiting	ORR 45 Complete response 0 Partial response 45 Stable disease 51 Progressive disease 2 Disease control rate 96	-	Nausea 54 (2) Diarrhea 51 (2) Vomiting 35 (2) Fatigue 32 (6) Increased ALT 20 (5) Increased AST 17 (5) Increased creatinine 15 (0) Decreased appetite 15 (0) QT prolongation 14 (3) Anemia 13 (2) Grade 5 TRAEs in two patients (pneumonitis, cardiac failure) Discontinuation due to TRAEs in 4.5%	30 August 2020 with a median follow-up time of 9.6 months
Adagrasib (MRTX849) +TNO155	NCT04330664 KRYSTAL-2	Phase 1/2 recruiting	-	-	-	-
Adagrasib (MRTX849) +pembrolizumab	NCT04613596 KRYSTAL-7	Phase 2 recruiting	-	-	-	-
GDC-6036 −/+atezolizumab −/+bevacizumab −/+erlotinib	NCT04449874	Phase 1a/1b recruiting	-	-	-	-
LY3499446 +/− abemaciclib/ erlotinib vs. docetaxel	NCT04165031	Phase 1 terminated due to toxicity	-	-	-	-