Mirati Therapeutics has taken the lid off updated data on KRAS inhibitor adagrasib in colorectal cancer. Having established itself as the front-runner in the space last year, the biotech has presented a new look at the phase 1/2 data that largely reaffirm the earlier findings.
One year ago, Mirati arrived at the European Society for Medical Oncology (ESMO) congress with data to suggest adagrasib has the edge over Amgen’s Lumakras in colorectal cancer. While Lumakras limped to a 7% overall response rate (ORR) in the indication, adagrasib triggered responses in 22% of the participants who were evaluable at the May 2021 cutoff.
Now, amid ongoing uncertainty about the accelerated approval pathway for adagrasib, Mirati will use ESMO 2022 to share updated data from the colorectal cancer cohort of its KRYSTAL-1 trial. The results in the third line and beyond population are close to a carbon copy of the 2021 presentation.
In the evaluable monotherapy cohort, which shrank from 45 to 43 participants between the two ESMO events, Mirati saw eight responses, resulting in an ORR of 19%. The biotech has around one year of extra follow-up, but the median duration of response (DOR) and progression-free survival (PFS) are practically unchanged from one year ago, clocking in at 4.3 months and 5.6 months, respectively.
Similarly, data on the cohort of patients who received adagrasib in combination with cetuximab, sold under the brand name Erbitux, hew closely to the 2021 results. Again, the number of evaluable patients has fallen, this time from 32 to 28. The ORR is up slightly, from 43% to 46%, and Mirati now has durability data, reporting a median DOR of 7.6 months and median PFS of 6.9 months.
Mirati is running a phase 3 clinical trial of the adagrasib-cetuximab combination in second-line colorectal cancer patients. The trial got underway 18 months ago and has a primary completion date of September 2023, according to ClinicalTrials.gov.
In theory, the KRYSTAL-1 data could support accelerated approval in third-line patients before Mirati has the phase 3 results, but the wait for clarity on that option has dragged on. Two months after ESMO 2021, Mirati CEO David Meek told investors to expect additional clarity on a potential pathway for accelerated approval in the first half of 2022. The plan is now to provide an update by the end of the year.
As Mirati works to determine the next steps, competitors are amassing on its flanks. Amgen, which has its own data to share at ESMO, kicked off a phase 3 combination trial in colorectal cancer earlier this year. Roche is also moving into position, with phase 1 solid tumor data on GDC-6036 planned for release at the conference.