Heavily pretreated patients may experience a response1,2
- At primary analysis (n=94; median follow-up 11.9 months): ORR: 34% (95% CI: 25-45)1
- At primary analysis (n=94; median follow-up 11.9 months): mDOR: 5.8 months (95% CI: 4.2-7.6). 31% of patients had a response duration of ≥6 months)1†
Median DOR: 5.8 months (95% CI: 4.2–8.5)
- 41% of patients had a response duration of ≥6 months3†
- 22% of patients had a response duration of ≥12 months3
CRC
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for colon and rectal cancers recommend adagrasib (KRAZATI) + cetuximab as a systemic therapy option for patients with KRAS G12C-mutated advanced CRC.4,5
*Tumor response was assessed by BICR. Data cutoff: April 30, 2024.
†Observed proportion of patients with duration of response beyond landmark time.
KRAZATI delivered a response in KRYSTAL-1 for KRAS G12C-mutated advanced CRC.
In non-comparative cohorts of the phase 1 and phase 2 KRYSTAL-1 trial, patients who received Krazati + cetuximab (pooled analysis phase 1/2; N=94) achieved 34% ORR, and patients who received Krazati monotherapy (phase 1; N=42) achieved 21% ORR.
Indication
KRAZATI® (adagrasib) in combination with cetuximab is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.
In a phase 1 cohort of KRYSTAL-1, KRAZATI plus cetuximab yielded a numerically higher ORR compared to a separate phase I cohort of patients with KRAS G12C–mutated mCRC receiving KRAZATI monotherapy (34% ORR for KRAZATI + cetuximab vs 21% for KRAZATI monotherapy, N=42; 95% CI: 10.3-36.8).
BICR=blinded independent central review; CI=confidence interval; CRC=colorectal cancer; CR=complete response; DOR=duration of response; mDOR=median duration of response; NCCN=National Comprehensive Cancer Network; ORR=objective response rate; PR=partial response.
References:
- KRAZATI®. Prescribing information. Princeton, NJ. Mirati Therapeutics, Inc., a Bristol Myers Squibb company; 2024.
- Yaeger R, Uboha NV, Klempner SJ, et al. Adagrasib + cetuximab for KRASG12C-mutated metastatic colorectal cancer: longer follow-up analysis from KRYSTAL-1. Poster presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium; January 23-25, 2025; San Francisco, CA and online.
- Data on file. BMS-REF-ADAG-0032. Princeton, NJ: Bristol-Myers Squibb Company; 2025.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 4, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 4, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.