The partial response rate reported Sunday from the high dose of Amgen’s KRAS inhibitor AMG 510 had nowhere to go but down, given that the 100% PR rate seen earlier this year was from just three patients. While the metric fell farther than investors expected, the company said it may seek approval based an ongoing Phase II study, which is using the dose.
Among 13 evaluable patients treated with the 960 mg high dose in the Phase I trial to treat KRAS G12C mutant advanced stage NSCLC, 54% (7/13) had a partial response. The remaining six patients had stable disease (46%) for a disease control rate of 100%.
Amgen Inc.’s previous report of partial responses in three out of three patients in the 960 mg cohort made a buzz at the American Society of Clinical Oncology (ASCO) meeting in June. On Sunday, the company said two of those patients had progressed.
Evercore ISI analyst Umer Raffat said in a note released ahead of the data that while it’s not realistic to expect 100% ORR, “I believe we can see more than 70% ORR” in the additional patients at 960 mg.
Amgen (NASDAQ:AMGN) shares were off $5.39 to $202.34 on Monday.
Across all doses, Amgen’s updated data were similar to the findings it presented at ASCO, where it said 10 patients had a PR rate of 50% and a stable disease rate 40%. One patient with a PR improved further to a complete response of the target lesions at week 18, after data cutoff (see “Promising ASCO Readout for AMG 510”).
The updated findings across all doses showed 23 evaluable patients had a PR rate of 48% (11/23) and stable disease was 48% (11/23). One patient had progressive disease for a disease-control rate of 96%.
The doses in the study ranged from 180 mg to 960 mg. The latter has gotten the most attention because it was selected as the Phase II dose.
There were no dose-limiting toxicities or treatment-related serious or fatal AEs.
Across all 11 patients with a PR, the median duration of treatment is 15.1 weeks with 8 of 11 patients continuing on the study.
“It is very early days at 960 mg, and we don’t have a firm estimate on durability,” spokesperson Trish Hawkins told BioCentury. “We only have two patients across the entire study whose initial CT response results could not be confirmed in the follow up scan.”
On an investor call to discuss the data, Amgen said that it had not yet been able to identify a pattern in response and number of prior therapies. Patients in the NSCLC cohort had a median of 3.5 prior therapies, ranging from one to eight.
Amgen presented the data at the World Conference on Lung Cancer in Barcelona.
Amgen said Sunday that the patient who had the complete response remains unchanged. The Phase II trial is enrolling, and the company expects data in early 2020. The company said on the investor call that it may seek approval for AMG 510 based on the Phase II data.
The KRAS G12C mutation occurs in about 14% of NSCLC patients. AMG 510 is an oral KRAS inhibitor that selectively and irreversibly binds to the mutant protein.
Until recently, KRAS had been difficult to target because of a lack of well-defined surface pockets for drug binding.
However, researchers started to make headway over the past five years, particularly with mutated KRAS G12C, which places a cysteine in the GTP-binding site that can be targeted (see “Covalent Hits on KRAS”).
While AMG 510 is the most advanced KRAS inhibitor, other companies have candidates in the clinic against the target.
MRTX849 from Mirati Therapeutics Inc. (NASDAQ:MRTX) is in Phase I/II testing to treat advanced solid tumors harboring KRAS G12C mutations. The company plans to present results this year. Mirati fell $4.57 to $82.70 Monday.
Amgen said it plans to present additional data across tumor types from the AMG 510 program at the European Society for Medical Oncology (ESMO), which kicks off Sept. 27.