- Merck's Keytruda (pembrolizumab) notched a first-of-its-kind victory on Tuesday, getting accelerated approval from the Food and Drug Administration as a treatment for tumors that demonstrate an uncommon mutation affecting the way in which they fix genetic mistakes.
- The new indication centers around cells that have deficient mismatch repair (dMMR) systems, meaning that they don't properly correct blunders made during DNA replication. The byproduct of a dMMR is a large amount of amino acid substitutions in the microsatellites — small, repeated DNA segments — of various proteins. Those oddly coded proteins can then tip off the immune system that something is wrong in the cell, a chain reaction that researchers have found particularly interesting as they look for new immuno-oncology therapies.
- Keytruda's now green lit for people with colorectal cancer or solid tumors that have dMMR or high levels of microsatellite instability, known as MSI-H. Patients must also have metastatic or inoperable forms of those cancers, and have shown disease progression after previously receiving another treatment.
Keytruda has racked up a host of indications since its initial approval in 2014. Just this year, the drug has secured approval as a first-line treatment for metastatic, non-squamous non-small cell lung cancer (NSCLC) regardless of PD-L1 expression, as a first-line and second-line medicine for some cases of locally advanced or metastatic urothelial carcinoma, and as a medication for refractory classical Hodgkin lymphoma.
Tuesday's nod is noteworthy because normally the FDA OKs cancer drugs that target a specific area of the body, such as breasts, prostate or head and neck. Now, there's a product that targets tumors based on similar characteristics, rather than its location — and validation around MSI-H's usefulness as a biomarker for cancer therapeutics.
"It is the first pan-cancer biomarker in the history of cancer treatment that defines or identifies patients that will benefit from a particular form of therapy regardless of the tissue of origin of the cancer," Drew Pardoll, director of the Johns Hopkins Bloomberg~Kimmel Institute and a collaborator of the Phase 2 trial testing Keytruda in this indication, told BioPharma Dive in an interview.
"When you take all of the cancers across the board, it's probably 75% to 80% of cancers that should be tested," Pardoll added. "But any cancer for which there is no accepted therapy that will give any benefit should be tested if they're one of those cancers. It's easier to find cancers that don't have this subset."
The FDA's approval hinged on five studies that tested Keytruda in a combined 149 patients with a variety of cancers, the most common of which were gastrointestinal cancers. The studies were uncontrolled; yet nearly 40% percent of participants had a complete or partial response in the form of tumor shrinkage — and 78 had that shrinkage last for at least six months.