ESMO21: Mirati's adagrasib continues to impress in colorectal cancer

Results published Friday ahead of presentation at the European Society for Medical Oncology (ESMO) congress showed an improving response rate for Mirati Therapeutics' adagrasib in patients with colorectal cancer harbouring a KRAS G12C mutation, which was even higher when the KRAS inhibitor was combined with Merck KGaA and Eli Lilly's EGFR inhibitor Erbitux (cetuximab).

Mirati previously disclosed data from 18 patients in the Phase I/II KRYSTAL-1, with adagrasib demonstrating a confirmed overall response rate (ORR) of 17% and disease control rate (DCR) of 94%. The latest update, based on 45 evaluable patients, showed that the ORR improved to 22%, including one unconfirmed partial response (PR), while the DCR was 87%.

Superior to Lumakras, although toxicity an issue

Meanwhile, the confirmed ORR in 28 evaluable patients treated with the combination of adagrasib and Erbitux was 39%, with a DCR of 100%. The data compare favourably to Amgen's Lumakras (sotorasib), which has shown a response rate of <10% in patients with KRAS G12C-mutated advanced colorectal cancer when used as a monotherapy, rising to 27% when combined with the EGFR inhibitor Vectibix (panitumumab).

However, the ESMO abstract indicated that grade 3/4 treatment-related adverse events (TRAEs) occurred in 30% of patients given adagrasib alone and in 16% of those receiving the drug in combination with Erbitux. Mirati added that TRAEs that led to treatment discontinuation occurred in 6% of patients who received adagrasib plus Erbitux, compared to none in the adagrasib monotherapy arm.

Mirati CEO Charles Baum said "it looks like we've gained quite a bit in efficacy and not really added much significant toxicity. So that's why, you know, that combination approach may end up being our fastest approach for accelerated approval." Baum noted that the results "support further study of adagrasib in KRAS-mutated colon cancer, including with our ongoing, global registrational Phase III trial, KRYSTAL–10, comparing adagrasib plus [Erbitux] to standard-of-care chemotherapy in second-line KRASG12C-mutated colorectal cancer."

Join FirstWord editors Michael Flanagan, Virginia Li and Simon King on Wednesday 22 September (3pm GMT / 10am EST) for a discussion on five key takeaways from the ESMO congress. Register for free here.


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