Table 2.
Summary of currently available data on combining KRAS G12C inhibitors with immune checkpoint inhibitors and chemotherapies.
| Combination (NCT number) | Phase | Population* | N | Toxicity data | Efficacy data | Reference |
|---|---|---|---|---|---|---|
| Pembrolizumab + adagrasib NCT04613596 (KRYSTAL-7) |
2 | Untreated advanced NSCLC | 148 | Common TRAE: nausea, diarrhea, AST/ALT increase Grade 5 TRAE: pneumonitis and pneumonia TRAE to d/c regimen: 4% for both, 6% for adagrasib, and 11% for pembrolizumab |
In PD-L1 ≥ 50% (N = 54) RR: 63% mPFS: not reached |
(38) |
| Pembrolizumab/atezolizumab + Sotorasib (lead-in and concurrent) NCT03600883, NCT04185883 (CodeBreaK 100/101) |
1b | Advanced NSCLC with no prior KRAS G12C treatment | 58 | G3-4 TRAE: 45% with lead-in, 72% with concurrent (most commonly AST/ALT increased) TRAE to d/c regimen: 24% with lead-in, 52% with concurrent |
RR (lead-in): 31% RR (concurrent): 28% mOS: 15.7m |
(39) |
| Pembrolizumab + MK1084 NCT05067283 |
1 | Untreated advanced NSCLC | 24 | Common TRAE: increased AST/ALT, diarrhea, pruritus G3-4 TRAE: 42% (AST/ALT increase most common: 13%) TRAE to d/c regimen: 25% |
RR: 71% | (40) |
| Carboplatin + pemetrexed + sotorasib NCT04185883 (CodeBreaK 101) |
1b | Advanced NSCLC | 38† | Common TRAE: neutropenia, anemia, thrombocytopenia G3-4 TRAE: 58% (most commonly neutropenia) TRAE to d/c regimen: 8% (first line) and 15% (second line) for sotorasib, 4% (first line) and 15% (second line) for carboplatin, and 12% (first line) and 23% (second line) for pemetrexed |
As first line (N = 20) RR: 65% As second line (N = 13) RR: 54% |
(41) |
| Carboplatin + pemetrexed + sotorasib jRCT2051210086 (SCARLET) |
2 | Untreated advanced NSCLC | 30 | Common TRAE: anemia, neutrophil count decreased, nausea, and platelet count decreased G3-4 TRAE: mostly hematological toxicities One treatment-related death from pneumonia |
RR: 88.9% mPFS: 5.7m |
(42) |
d/c, discontinue; G3, 4, and 5, grades 3, 4, and 5; mOS, median overall survival (months); mPFS, median progression-free survival (months); N, number of participants; NSCLC, non-small cell lung cancer; PR, partial response; RR, response rate; SD, stable disease; TRAE, treatment-related adverse events.
*All participants should have KRAS G12C mutation.
†Twenty-five patients were in the first-line setting, and 13 patients were in the second-line setting.