Amgen’s KRAS inhibitor made a splash at this year’s American Society of Clinical Oncology (ASCO) annual meeting, and with good reason—it was the first drug of its class to post clinical data. The phase 1 data showed that the drug, AMG 510, shrank lung tumors, but not colorectal tumors, merely stopping their growth. Sanket Agrawal, who heads the KRAS program at Amgen, noted that all but one of the colorectal cancer patients had been treated with the two lowest doses of the drug, hinting that higher doses might do even better.
Now, though, the Big Biotech has positive updates. Amgen reported in its second-quarter earnings presentation Tuesday that AMG 510 shrank tumors in patients with colorectal cancer and cancer of the appendix. Details were thin, but the news is a win for the drug, which was tested in 19 patients with colorectal cancer and 2 patients with appendiceal cancer.
"We can confirm these responses are seen in the higher doses," said an Amgen spokesperson by email Tuesday evening.
"With regard to colorectal, the majority of patients that we're reporting going forward will have been treated at 960 mg," said Amgen CEO Bob Bradway on the earnings call. The study tested four doses: 180 mg, 360 mg, 720 mg and maxing out at 960 mg.
The target dose for colorectal patients is 960 mg, but R&D chief David Reese acknowledged that this could still change.
"I think we'll look for insights from that cohort. It remains early in this development program. And with these drugs of course, there is often tweaking of dosing and scheduling as you go along. But I would say that at this point, 960 is our target dose," Reese said. "We will assess emerging data to see if we want to explore some other doses and schedules going forward."
The revelation is “By FAR the biggest disclosure on AMGN earnings,” wrote Evercore ISI analyst Umer Raffat in a note.
“AMGN's KRAS is the most impt program in their pipeline and a potential multi-billion mkt. Recall that there were no responses for [colorectal cancer] back at ASCO—and this had left an opening from the competitors (e.g. Mirati data this fall and JNJ likely next year). Also recall that AMGN had 3/3 lung cancer pats show a response at the high dose," Raffat wrote.
The non-small cell lung cancer (NSCLC) patients were the headline at ASCO. AMG 510 shrank tumors in five of the 10 evaluable NSCLC patients and stopped tumor growth in another four, showing it could control the disease in 90% of patients. As for the colorectal cancer patients, nearly three-quarters of the evaluable patients achieved stable disease, meaning their tumors had stopped growing.
In this study, Amgen tested AMG 510 as a single agent to be used after the patient has exhausted other treatments. But it’s looking to move into earlier lines of treatment and plans to start a phase 1b study combining AMG 510 with checkpoint inhibitors.
"In terms of potential registration plans, we would assume that lung cancer will be the lead indication going forward. As I mentioned in the coming days, we will be enrolling in the phase 2 portion of that program," Bradway said on the call. "We're moving very, very rapidly and we'll provide updates on that particular pathway as we go forward."
Editor's note: This story has been updated to include information from Amgen's second-quarter 2019 earnings call.