FDA Grants Keytruda Accelerated Approval for Solid Tumors with Common Biomarker

For the first time, the FDA has granted accelerated approval to pembrolizumab (Keytruda) to treat patients based on a common biomarker, rather than the area of the body where the tumor originated.

Pembrolizumab is designed to target the PD-1/PD-L1 cellular pathway to help the body’s own immune system fight cancer cells.

It is indicated for the treatment of adults and pediatric patients with unresectable or metastatic solid tumors that have been identified as having the biomarker microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), according to a press release.

The approval covers patients with solid tumors that progressed following prior treatment, and who do not have satisfactory alternative treatment options, as well as for patients with colorectal cancer that progressed following treatment with certain chemotherapy drugs.

Tumors containing MSI-H and dMMR have abnormalities that affect the proper repair of DNA inside the cell. Tumors containing these biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. They can also appear in the breast, prostate, bladder and thyroid gland, although it is less common.

An estimated 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors, according to the release.

The safety and efficacy of pembrolizumab for this indication was studied in patients with MSI-H or dMMR solid tumors who were enrolled in 1 of 5 uncontrolled, single-arm clinical trials.

Across the 5 trials, a total of 15 cancer types were identified among the 149 patients, with the most common being colorectal, endometrial, and other gastrointestinal cancers. The primary endpoint was overall response rate and durability of response.

The results of the trials showed that of the 149 patients administered pembrolizumab, 39.6% had a complete or partial response. Of those patients, 78% had a response that lasted for 6 months or longer.

The most common adverse events (AEs) include fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea. Serious AEs are pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

Complications or death related to allogeneic hematopoietic stem cell transplantation after taking pembrolizumab have also occurred, the release noted.

“This is an important first for the cancer community,” Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products, FDA Center for Drug Evaluation and Research, director of the FDA’s Oncology Center of Excellence, said in a release. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—–for example, lung or breast cancers. We have no approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”