First-line adagrasib (ADA) + pembrolizumab (PEMBRO) brings a chemo-free option to the frontline for KRASG12C-mutant NSCLC!
Presented by Dr. Pasi Jänne (Dana-Farber)
Oral Abstract 8500 | ASCO LCSM
Key results (n = 149):
- ORR: 44%
- DCR: 81%
- mPFS: 11.0 months
- mDOR: 26.3 months (12-month DOR rate = 73%)
- mOS: Not reached in PD-L1 ≥50%
PD-L1 subgroup OS:
- TPS ≥50% → Not Reached
- TPS 1–49% → 14.3 months
- TPS <1% → 15.5 months
Safety:
- Grade ≥3 TRAEs in 58%
- Most common: nausea (56%), diarrhea (47%), ALT increase (40%)
- Immune AEs: pneumonitis (12%), hypothyroidism (7%)
- Hepatic TRAEs in 59%, mostly mild/moderate
Takeaways:
- Durable responses in first-line setting
- Benefit enriched in PD-L1 ≥50%
- ADA + PEMBRO shows real potential as a chemo-sparing regimen
- Escalation (e.g., adding chemotherapy) may be needed for lower PD-L1 expression
Now enrolling phase 3:
- KRYSTAL-7 (ADA + PEMBRO vs PEMBRO)
- KRYSTAL-4 (ADA + PEMBRO + chemotherapy).”
More posts featuring ASCO25.