FDA Actions & Updates
The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Thursday, April 27, 2017

​​The FDA expanded the approved use of regorafinib to include treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with the drug sorafenib. This is the first FDA-approved treatment for a liver cancer in almost a decade.

"Limited treatment options are available for patients with liver cancer," said Richard Pazdur, M.D., Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and director of the FDA's Oncology Center of Excellence. "This is the first time patients with HCC have had an FDA-approved treatment that can be used if their cancer has stopped responding to initial treatment with sorafenib."

According to the NCI, approximately 40,710 people will be diagnosed with liver cancers in 2017 and approximately 28,920 will die of these diseases. HCC originates in the liver and is the most common form of liver cancer.

Regorafinib is a kinase inhibitor that is also approved to treat colorectal cancer and gastrointestinal stromal tumors that are no longer responding to previous treatments.

The safety and efficacy of regorafinib for treatment of HCC were studied in a randomized trial of 573 patients with HCC whose tumors had progressed after receiving sorafenib. The trial measured the overall survival, progression-free survival, and overall response rate. The median overall survival for patients taking regorafinib was 10.6 months, compared to 7.8 months for patients taking a placebo. The median progression-free survival for patients taking regorafinib was 3.1 months compared to 1.5 months for patients taking a placebo. The overall response rate was 11 percent, compared to 4 percent of patients taking placebo.

Common side effects of include pain (including gastrointestinal and abdominal pain), hand-foot skin reaction, fatigue, diarrhea, decreased appetite, hypertension, infection, dysphonia, hyperbilirubinemia, fever, mucositis, weight loss, rash, and nausea. Regorafinib is associated with serious risks, including hepatotoxicity, infections, hemorrhage, gastrointestinal perforation or fistula, dermatologic toxicity, hypertension, cardiac ischemia and infarction, reversible posterior leukoencephalopathy syndrome), and wound healing complications.

Women who are pregnant or breastfeeding should not take regorafinib because it may cause harm to a developing fetus or a newborn baby. Women and men who are taking regorafinib should use effective contraception during and for 2 months after taking the final dose.

This regorafinib application was granted Priority Review designation. This indication also received Orphan Drug designation.

Monday, April 10, 2017

​The FDA has authorized the initiation of a phase I clinical trial with MVT-1075 as a therapeutic treatment for pancreatic cancer. MVT-1075 (177Lu-CHX-A″-DTPA-HuMab5B1) is a novel, fully human antibody radio-immunotherapy (RIT). The trial will be initiated among patients with recurrent pancreatic cancer and other CA19-9 positive malignancies in the first half of 2017.

The MVT-1075 RIT agent combines the targeting specificity of the HuMab-5B1 antibody for an antigen over-expressed on pancreatic cancer and other CA19-9 positive cancers with 177Lutetium to target delivery of therapeutic radiation to cancer cells. Preclinical studies have demonstrated marked suppression and in some instances regression in xenograft animal models of pancreatic cancer, potentially making it an important new therapeutic agent in the treatment of pancreatic cancer and other cancers expressing the same antigen, CA19-9.

In this initial phase I trial, the safety, dosimetry, and pharmacokinetics of MVT-1075 will be evaluated. Patients enrolled in the study will have been diagnosed with recurrent locally advanced or metastatic pancreatic ductal adenocarcinoma or other CA19-9 positive malignancies. Patient disease status will be evaluated based on tumor measurements using RECIST 1.1 criteria.

Monday, April 10, 2017

Xermelo (telotristat ethyl) tablets in combination with somatostatin analog (SSA) therapy was recently approved by the FDA for the treatment of adults with carcinoid syndrome diarrhea that SSA therapy alone has inadequately controlled.

Carcinoid syndrome is a cluster of symptoms sometimes seen in people with carcinoid tumors. These tumors are rare and often slow-growing. Most carcinoid tumors are found in the gastrointestinal tract. Carcinoid syndrome occurs in less than 10 percent of patients with carcinoid tumors, usually after the tumor has spread to the liver. The tumors in these patients release excess amounts of the hormone serotonin, resulting in diarrhea. Complications of uncontrolled diarrhea include weight loss, malnutrition, dehydration, and electrolyte imbalance.

Xermelo, in a regimen with SSA therapy, is approved in tablet form to be taken orally three times daily with food. Xermelo inhibits the production of serotonin by carcinoid tumors and reduces the frequency of carcinoid syndrome diarrhea.

The safety and efficacy of xermelo was established in a 12-week, double-blind, placebo-controlled trial in 90 adult participants with well-differentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea. These patients were having between four and 12 daily bowel movements despite the use of SSA at a stable dose for at least 3 months. Participants remained on their SSA treatment and were randomized to add placebo or treatment with xermelo three times daily. Those receiving xermelo added on to their SSA treatment experienced a greater reduction in average bowel movement frequency than those on SSA and placebo. Specifically, 33 percent of participants randomized to add xermelo on to SSA experienced an average reduction of two bowel movements per day compared to 4 percent of patients randomized to add placebo on to SSA.

The most common side effects include nausea, headache, increased levels of the liver enzyme gamma-glutamyl transferase, depression, peripheral edema, flatulence, decreased appetite, and fever. Xermelo may cause constipation, and the risk of developing constipation may be increased in patients whose bowel movement frequency is less than four bowel movements per day. Patients treated with a higher than recommended dosage developed severe constipation in clinical trials. One patient required hospitalization and two other patients developed complications of either intestinal perforation or intestinal obstruction. Patients should be monitored for severe constipation.

The FDA granted this application Fast Track Designation and priority review. The drug also received Orphan Drug Designation, which provides incentives to assist and encourage the development of drugs for rare diseases.​

Monday, April 10, 2017

The FDA awarded Fast Track designation to ImmunoPulse IL-12, a potentially first-in-class, intratumoral anti-cancer gene therapy that expresses interleukin-12 (IL-12) for the treatment of metastatic melanoma, following progression on pembrolizumab or nivolumab.

The PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study) will be a phase IIb, Simon two-stage, non-comparative, open-label, single-arm, multicenter study of ImmunoPulse IL-12 (intratumoral pIL-12 plus electroporation) in combination with an IV anti-PD-1 antibody in patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as stage III or IV.

Eligible patients will be those with stage III/IV metastatic melanoma who are progressing or have progressed according to RECIST v1.1 guidelines on, or within, 24 weeks of receiving approved anti-PD-1 antibodies on either pembrolizumab or nivolumab treatment (either as monotherapy or in combination with another approved checkpoint inhibitor).

The primary endpoint for this registration-directed trial will be overall response rate at 24 weeks with secondary endpoints of best overall response rate, duration of response, median progression-free survival, and overall survival. This clinical trial is planned to initiate in the first half of 2017.

Thursday, April 6, 2017

Avelumab has been granted accelerated approval by the FDA for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC), including those who have not received prior chemotherapy.

This is the first FDA-approved treatment for metastatic MCC. Avelumab targets the PD-1/PD-L1 pathway; by blocking these interactions, avelumab may help the body's immune system attack cancer cells.

"While skin cancer is one of the most common cancers, patients with a rare form called Merkel cell cancer have not had an approved treatment option until now," said Richard Pazdur, MD, Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and Director of the FDA's Oncology Center of Excellence. "The scientific community continues to make advances targeting the body's immune system mechanisms for the treatment of various types of cancer. These advancements are leading to new therapies—even in rare forms of cancer where treatment options are limited or non-existent."

According to the NCI, approximately 1,600 people in the U.S. are diagnosed with MCC every year. While the majority of patients present with localized tumors that can be treated with surgical resection, approximately half of all patients will experience recurrence, and more than 30 percent will eventually develop metastatic disease. In patients with metastatic MCC, the cancer has spread beyond the skin into other parts of the body. 

The approval of avelumab was based on data from a single-arm trial of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen. The trial measured the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and, for patients with a response, the length of time the tumor was controlled (duration of response). Of the 88 patients who received avelumab in the trial, 33 percent experienced complete or partial shrinkage of their tumors. The response lasted for more than six months in 86 percent of responding patients and more than 12 months in 45 percent of responding patients.

Common side effects of avelumab include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, and peripheral edema. The most common serious risks of avelumab are immune-mediated, such as pneumonitis, hepatitis, colitis, endocrinopathies, and nephritis. In addition, there is a risk of serious infusion-related reactions. Patients who experience severe or life-threatening infusion-related reactions should stop using avelumab. Women who are pregnant or breastfeeding should not take avelumab because it may cause harm to a developing fetus or a newborn baby.

The FDA granted this application Priority Review and Breakthrough Therapy designation; Avelumab also received Orphan Drug designation.​