Piotr Wysocki, Professor of Medicine and Head of the Department of Oncology at Jagiellonian University Hospital, shared on LinkedIn:

“Results of a KRYSTAL-1, phase I/II trial have just been published in Cancer Discovery by Yaeger R. The study enrolled 94 patients with KRAS G12C-mutated metastatic colorectal cancer who were treated across phase I (n=32) and phase II (n=62)  cohorts. Most of the patients (91.5%) received at least 2 lines of previous palliative treatment (containing  fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF agent)

With a median follow-up of 11.9 months, the overall response rate (primary endpoint) was 34%, and disease control rate (DCR) – 85.1%. The median duration of response was 5.9 months (95%CI 4.2-7.6), and the median PFS and OS were 6.9 months and 15.9 months, respectively. Continued tumor control was observed in many patients receiving treatment beyond progression, with tumor shrinkage observed versus baseline at the first post-progression in 54.5% of patients continuing Adagrasib plus Cetuximab.

The most frequent treatment-related adverse events (TRAEs) with Adagrasib plus Cetuximab included nausea (60.6%), vomiting (51.6%), diarrhea (48.9%), and dermatitis acneiform (47.9%; Table  3). Grade 3–4 treatment related adverse events occurred in 27.7% of patients; there were no grade 5 TRAEs. TRAEs led to Adagrasib dose reductions in 29.8%.

Despite the fact that resistance to KRAS inhibitors is a common and early-occurring phenomenon, the KRYSTAL-1 study provides a very interesting observation that continuous administration of adagrasib may have a significant positive impact on long-term outcomes.”

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Source: Piotr Wysocki/LinkedIn