Mirati Therapeutics has spent 2021 watching Amgen blast past it to win the race to bring a KRAS drug to market in lung cancer. Yet, with Amgen’s Lumakras underwhelming in colorectal cancer, Mirati still has a shot at carving out a niche.
The small biotech rocked up to this year’s European Society of Medical Oncology (ESMO) congress with data to make its case.
Amgen previously linked Lumakras to an overall response rate (ORR) of 7% in colorectal cancer, well below the level that won it approval in non-small cell lung cancer. Mirati’s adagrasib was performing better than Lumakras at its previous data drop, with the usual caveats about cross-trial comparisons, but at 17% the ORR still had ample room for improvement. The biotech used a late-breaker at ESMO to share the latest data.
As of May 25, the response rate in the 45 evaluable patients who received adagrasib as a single agent stood at 22%. The 10 patients listed as responders include one person with an unconfirmed partial response who remains on study. Absent that unconfirmed response, the ORR would be 20%. Median duration of response was 4.2 months.
Mirati has previously said (PDF) an ORR of 20% and median duration of four months are the threshold to potentially seek accelerated approval of adagrasib in colorectal cancer. The data in the ESMO abstract put it over that bar—but only by a whisker.
A small percentage of colorectal cancer patients have KRAS G12C mutations, leading Mirati to put the size of the patient population across the U.S. and Europe at around 20,000 people. That makes for a far smaller market than non-small cell lung cancer but still represents an opportunity that may be wide open to Mirati given Amgen’s struggles in the indication.
Mirati also used ESMO to share an update on patients who have received adagrasib in combination with cetuximab, the drug also known as Erbitux. The response rate in the 28 evaluable patients who received the combination was 43%, including two people with unconfirmed partial responses. After the July 9 data cutoff, follow-up scans confirmed one response but the other patient progressed.
The findings offer encouragement for Mirati as it enrolls second-line colorectal cancer patients in a phase 3 trial of adagrasib in combination with cetuximab. Mirati has penciled in a September 2023 primary completion date for the 420-subject randomized clinical trial.
Amgen touted its own combination therapy data at ESMO but its numbers still lag those posted by Mirati. The response rate in colorectal cancer patients who received Lumakras in combination with EGFR inhibitor Vectibix was 27%, compared to 10% in the people who got the KRAS drug alone.