Amgen caught the cancer field's attention this summer with early results showing one of its drugs can shrink lung tumors driven to growth by a commonly mutated gene.
But replicating that efficacy in colon cancer may be more difficult, according to new data set to be presented Saturday at the European Society of Medical Oncology's annual meeting in Barcelona, Spain.
Only one of 29 patients with colorectal cancer experienced a partial response to treatment, while tumors in 22 others were judged stable. The remaining six had progressive disease, study investigators reported.
By comparison, results presented in September showed Amgen's drug reduced tumor size in 11 of 23 lung cancer patients — a response rate that excited oncologists and raised expectations on Wall Street of a potentially multibillion dollar market opportunity.
Called AMG 510, the treatment is aimed at protein produced by mutated KRAS, a so-called oncogene found in many lung, colon and pancreatic tumors. Enthusiasm is high because decades of research have failed to produce a promising clinical candidate, never mind an approved KRAS blocker.
The specific type of KRAS alteration that AMG 510 targets is present in roughly 13% of lung cancers and between 3% and 5% of colorectal cancers, according to estimates cited by Amgen.
Following promising data in June and September, the California-based biotech forged quickly ahead with AMG 510 and is now enrolling a Phase 2 study that could support submission to the Food and Drug Administration, should it prove successful.
The ESMO update, however, suggests the story could be different in colorectal cancer than in lung.
"For colorectal cancer, the idea of a single Achilles heel is more elusive than in other diseases," said Greg Friberg, Amgen's head of global development for oncology, in an interview ahead of the conference.
"We fully expect these patients to have other driver mutations," he added, giving alterations in the p53 and APC genes as examples.
Results among treated colorectal cancer patients could change, as all but one given the highest and most effective dose of AMG 510 began treatment since June. With more time, patients currently considered stable could experience tumor reductions significant enough to classify as a response.
A targeted KRAS drug with a response rate of 15% in second-line treatment of colorectal cancer could be approvable, suggested Jefferies analyst Michael Yee in a client note earlier this month. More than 80% of patients in Amgen's study received more than two prior therapies.
The drugmaker plans to soon start a combination study testing AMG 510 together with a MEK inhibitor to explore whether two drugs could work better together — a common approach that's proved effective for other treatment classes like BRAF inhibitors.
One patient with appendiceal cancer also experienced a partial response to AMG 510.
Importantly, Amgen's update at ESMO offered further reassurance that AMG 510 is well-tolerated, including at the 960 mg once daily dose the company's chosen to take forward. Across 76 treated patients, no dose-limiting toxicities were observed and no trial participants stopped treatment due to a side effect linked to the drug.
Six people on the study reported incidents of diarrhea or anemia that were classified as Grade 3. All other adverse events were rated Grade 1 or 2.
Looking ahead, the most significant question for Amgen will be how durable responses to AMG 510 prove to be. Follow-up remains limited thus far, so it's hard to draw conclusions from results the company's presented.
Investors and specialists recently polled by Cowen, an investment bank, thought responses lasting between six or seven months would be meaningful for a second-line treatment in KRAS-driven lung cancer. As of July 17, 52 of the 76 treated patients remained on AMG 510, Amgen said.
Since first impressing with the drug at the American Society of Clinical Oncology meeting in June, Amgen has enjoyed a rare moment in the cancer spotlight.
It may soon have to share, as initial results are expected later this year from small biotech Mirati Therapeutics, which is taking a similar approach to targeting KRAS as Amgen. Further down the road are data from a drug Johnson & Johnson licensed from Wellspring Biosciences.