- Combining Amgen's KRAS-blocking drug Lumakras with an older targeted therapy appeared to result in a higher rate of treatment responses among patients with advanced colon cancer than was previously reported for Lumakras alone, spurring the biotech company to launch a larger Phase 3 trial of the drug pairing.
- The new results, announced by Amgen Thursday ahead of a presentation at the European Society of Medical Oncology's virtual annual meeting, are from an early study that tested Lumakras together with Vectibix, an approved colon cancer drug also developed by Amgen.
- The data showed treatment shrank tumors in seven, or 27%, of 26 previously treated patients with KRAS-mutated metastatic colorectal cancer. That response rate, while modest, is higher than the 9.7% rate Amgen previously reported in a separate group testing Lumakras alone.
Lumakras is the first drug ever approved that can block mutations on a cancer-linked gene called KRAS that's for decades evaded researchers' best efforts to target it. Amgen won Food and Drug Administration approval for the drug in May based on results that showed treatment could shrink advanced lung tumors in roughly a third of patients.
Data in colorectal cancer have been much less impressive, however, leading the company to decide against advancing the drug as a monotherapy for the indication.
The story may be different with combination treatment, however, which Amgen has been studying in lung, colon and other solid tumors, using a wide range of partner therapies.
The early cut of data reported Thursday appears to have encouraged the drugmaker enough for it to green light a larger Phase 3 trial of Lumakras and Vectibix, even as it explores other drug pairings.
All told, 31 patients with metastatic colorectal cancer positive for the specific KRAS mutation Lumakras targets were included in the Phase 1b/2 cohort. All had been treated with at least one prior round of cancer therapy, although some had received as many as 10 prior lines of treatment.
There were no dose-limiting toxicities reported, although four participants experienced more severe treatment-related side effects.
The 27% response rate, while promising, comprises both confirmed and unconfirmed responses. Measured only on the former, the response rate was only 15%, although that could change as investigators in the study complete follow-up scans of patients' tumors.
As the data is from a single-arm study with no control group, it's also unclear how much Lumakras is driving added benefit. Vectibix is approved to treat colorectal cancer, but was not found effective for treating tumors driven by mutations in RAS genes, including some KRAS mutations.
"Although Vectibix isn't exactly considered the most active drug, single agent response data in relapsed/refractory CRC can readily be found in the 30% range," wrote Brian Skorney, an analyst at Baird, in a Sept. 16 note to clients. "Apples can't be compared to oranges, but given this context, it is hard to see an argument that today's results provide evidence that Lumakras is adding anything significant to Vectibix."
Amgen, by contrast, cited data indicating response rates in previously treated advanced colorectal cancer can be as low as 2%.
KRAS mutations are thought to occur in between 3% to 5% of colorectal cancers, making the market opportunity much smaller than in lung cancer.
Amgen could also face competition. Mirati Therapeutics, a smaller biotech developer of an experimental KRAS-blocking drug, is expected to present more data on its therapy adagrasib in colorectal cancer at the ESMO meeting.