When the FDA last week approved Merck’s cancer drug pembrolizuamb (Keytruda) for tumors with a specific genetic signature, regardless of what body part they originated in, it was a watershed moment for oncology and a victory for the concept of precision medicine.
But Merck isn’t alone; others are following suit with similar plans, and their progress is worth watching. One of the closest to the finish line is a four-year-old company named Loxo Oncology. Cancer experts believe that the data the company is presenting this morning at the American Society of Clinical Oncology not only demonstrate the potential of one promising new drug, but also represent another step forward for targeted cancer drugs as a class, which could in turn spur broader adoption of cancer genetic tests.
“We’re at a time where we’re realizing the potential of personalized medicine,” says Sumanta Pal, a medical oncologist at City of Hope in Duarte, CA, who isn’t associated with Merck or Loxo. “I truly feel that the data that’s emerged [from Merck and Loxo] are really going to drive increased utilization of genomic testing, and in many cases, I think that’s entirely appropriate.”
Loxo (NASDAQ: [[ticker:LOXO]]), of Stamford, CT, and South San Francisco, CA, reports this morning that 78 percent of the 55 total patients in three separate clinical trials of its drug, larotrectinib, have responded to treatment, meaning their tumors at least partially shrunk.
What makes those numbers particularly significant is Loxo enrolled patients with 17 different types of cancer—among them kidney, bladder, stomach, and lung—and found consistent results, according to CEO Josh Bilenker. These studies, called “basket” trials, took on patients with different cancers that share one important commonality: a genetic alteration known as a TRK fusion that Loxo’s drug is designed to target. The abnormality is present in 0.5 percent to 1 percent of solid tumors, he says.
“Simply put, larotrectinib is highly effective in patients with TRK fusions regardless of cancer type, and that’s a statement that really until recently we haven’t been able to make about any cancer therapy,” says David Hyman, a medical oncologist at Memorial Sloan Kettering Cancer Center and the principal investigator in the trials.
The most common side effects seen were dizziness, nausea, and fatigue. Though seven patients had their dose lowered because of side effects, none stopped treatment, which Hyman called “incredibly unusual” for a cancer drug trial.
The idea of targeted cancer therapies isn’t new. Drugs like imatinib (Gleevec), trastuzumab (Herceptin), vemurafenib (Zelboraf), and crizotinib (Xalkori) were approved many years ago for patients who have a particular type of cancer—lung cancer for crizotinib, for instance—and test positive for a specific molecular marker, like a genetic mutation or overexpression of a particular protein.
These drugs have made it common practice for, say, melanoma patients to get tested for a BRAF mutation (the target of vemurafenib), or breast cancer patients to be tested for expression of the HER2 protein (trastuzumab), and were thus important steps forward for targeted cancer medicines. Now better, cheaper sequencing technologies, more insight into tumor genetics, and creative clinical trial designs are leading to more efforts to try to see if these and other molecular signatures can impact many cancers, not just a few.
In 2015, for example, researchers conducted a basket study of the melanoma drug vemurafenib in a variety of cancers. Earlier this year, Hyman was an investigator in a basket trial testing the experimental Puma Biotechnology (NASDAQ: [[ticker:PUMA]]) drug neratinib, which is currently under an FDA review for HER2-positive breast cancer patients. Both studies produced mixed results, but there are others ongoing, like the 30-arm NCI-Match trial that began in 2015 that includes patients with lymphomas, solid tumors, and myelomas. And like Loxo, San Diego, CA-based Ignyta (NASDAQ: [[ticker:RXDX]]) is aiming for a tissue-agnostic approval of a drug, entrectinib, though its drug targets both TRK fusions and other mutations.
“If the biology supports a tumor-agnostic approach,” says Hyman, “then I think you’re going to be seeing more and more companies and investigators that are willing to take that risk and actually engage in this newer paradigm of drug development.”
Based on the data it already has in hand, Loxo aims to
