FDA Actions & Updates

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

Friday, September 14, 2018

The FDA recently approved moxetumomab pasudotox-tdfk injection for IV use for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin and is the first of this type of treatment for patients with HCL.

"[Moxetumomab pasudotox-tdfk] fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies," said Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "This therapy is the result of important research conducted by the NCI that led to the development and clinical trials of this new type of treatment for patients with this rare blood cancer."

The efficacy of moxetumomab pasudotox-tdfk was studied in a single-arm, open-label clinical trial of 80 patients who had received prior treatment for HCL with at least two systemic therapies, including a purine nucleoside analog. The trial measured durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR. Thirty percent of patients in the trial achieved durable CR, and the overall response rate was 75 percent.

Common side effects of moxetumomab pasudotox-tdfk include infusion-related reactions, swelling caused by edema, nausea, fatigue, headache, pyrexia, constipation, anemia, and diarrhea.

The prescribing information for moxetumomab pasudotox-tdfk includes a Boxed Warning to advise health care professionals and patients about the risk of developing capillary leak syndrome. Symptoms of capillary leak syndrome include difficulty breathing, weight gain, hypotension, or swelling of arms, legs and/or face. The warning also notes the risk of hemolytic uremic syndrome. Patients should be made aware of the importance of maintaining adequate fluid intake, and blood chemistry values should be monitored frequently. Other serious warnings include: decreased renal function, infusion-related reactions, and electrolyte abnormalities. Women who are breastfeeding should not be given moxetumomab pasudotox-tdfk.

The FDA granted this application Fast Track and Priority Review designations. Moxetumomab pasudotox-tdfk also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Monday, August 27, 2018

The FDA approved ibrutinib in combination with rituximab for the treatment of Waldenström's macroglobulinemia (WM). The approval expands the label for ibrutinib in WM beyond its current approved use as a monotherapy to include combination use with rituximab. This approval represents the first approved non-chemotherapy combination option for the treatment of WM.

Ibrutinib first received FDA approval in WM as a monotherapy in January 2015 via the Breakthrough Therapy Designation pathway, making it the first FDA-approved therapy for the disease.

"The combination of ibrutinib and rituximab provides health care professionals with a new treatment option for patients living with this serious blood cancer," said Lia Palomba, MD, hematologist-oncologist at Memorial Sloan-Kettering Cancer Center, New York, and iNNOVATE study investigator. "Before ibrutinib, there were no FDA-approved treatment options for patients with Waldenström's macroglobulinemia, a disease first acknowledged nearly 75 years ago. Today, ibrutinib continues to provide an important therapeutic approach in the treatment of this complex disease."

This approval is based on results from the randomized, double-blind, placebo-controlled iNNOVATE study (PCYC-1127), the largest phase III study of a non-chemotherapy combination in WM patients. The iNNOVATE study evaluated ibrutinib in combination with rituximab versus placebo plus rituximab in 150 patients with either relapsed/refractory (r/r) disease or previously untreated WM.

At a median follow up of 26.5 months, a significant improvement in the Independent Review Committee (IRC)-assessed primary endpoint of progression-free survival (PFS) was seen with ibrutinib plus rituximab when compared with placebo plus rituximab (30-month PFS rates were 82% vs. 28%, respectively). Patients in the ibrutinib plus rituximab treatment arm experienced an 80 percent reduction in relative risk of disease progression or death compared with patients treated with placebo plus rituximab (hazard ratio=0.20; confidence interval, 0.11-0.38, p<0.0001). The data were presented in an oral session at the 2018 ASCO Annual Meeting, selected for Best of ASCO 2018 Meetings, and simultaneously published in The New England Journal of Medicine (2018; doi:10.1056/NEJMoa1802917).

"Results from iNNOVATE showed significant improvement in progression-free survival at 30 months and demonstrated the superiority of ibrutinib plus rituximab over rituximab monotherapy in Waldenström's macroglobulinemia," said Meletios A. Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and iNNOVATE lead study investigator. "Based on these results, ibrutinib in combination with rituximab may be considered as a first- and second-line option for appropriate people diagnosed and living with WM."

The most common adverse reactions (occurring in 20% or more of patients) of all grades in patients treated with ibrutinib plus rituximab in the iNNOVATE study were bruising (37%), musculoskeletal pain (35%), hemorrhage (32%), diarrhea (28%), rash (24%), arthralgia (24%), nausea (21%), and hypertension (20%). Grade 3 or 4 infusion-related reactions were observed in 1% of patients treated with ibrutinib plus rituximab.

The recommended dose of ibrutinib for WM is 420 mg orally once daily until disease progression or unacceptable toxicity as a single agent or in combination with rituximab. When administering ibrutinib in combination with rituximab, consider administering ibrutinib prior to rituximab when given on the same day.

Friday, August 17, 2018

Nivolumab received approval from the FDA as the first and only immuno-oncology treatment option for patients with metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.

Approval for this indication has been granted under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

This approval for nivolumab in patients with SCLC whose cancer has progressed after two or more prior lines of therapy was granted priority review from the FDA.

The approval was based on data from the SCLC cohort of the ongoing phase I/II CheckMate-032 study evaluating nivolumab in patients who experienced disease progression after platinum-based chemotherapy. Of 109 patients receiving nivolumab after platinum-based chemotherapy and at least one other prior line of therapy, 12 percent (n=13/109; 95% CI: 6.5-19.5) responded to treatment based on assessment by a Blinded Independent Central Review (BICR), regardless of PD-L1 expression.

Twelve patients had a partial response (11%), and one patient had a complete response (0.9%). Among these responders, the median DOR was 17.9 months (95% CI: 7.9-42.1; range: 3.0-42.1 months). Nivolumab was discontinued in 10 percent of patients, and one dose was withheld in 25 percent of patients for an adverse reaction. Serious adverse reactions occurred in 45 percent of patients. The approved dosing for nivolumab in this indication is 240 mg administered every 2 weeks by IV infusion until disease progression or unacceptable toxicity.

Nivolumab is associated with the following Warnings and Precautions: immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.

"While Immuno-Oncology innovations have dramatically changed how oncologists approach certain cancers, we have had limited progress for patients with small cell lung cancer," said Leora Horn, MD, MSc, Associate Professor of Medicine, Ingram Associate Professor of Cancer Research, Director of the Thoracic Oncology Program and Assistant Vice Chairman for Faculty Development, Vanderbilt University Medical Center. "[This] approval of nivolumab is particularly exciting considering it is the first checkpoint inhibitor approved for these specific patients, and now we can finally treat this devastating disease from a different angle."

"Small cell lung cancer can be a very challenging disease, particularly for those who have already been through multiple types of treatment, as most patients relapse within a year of diagnosis," noted Andrea Ferris, President and Chairman of LUNGevity Foundation. "This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options."

Wednesday, August 8, 2018

The FDA approved mogamulizumab-kpkc injection for intravenous use for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. This approval provides a new treatment option for patients with MF and is the first FDA approval of a drug specifically for SS.

"Mycosis fungoides and Sézary syndrome are rare, hard-to-treat types of non-Hodgkin lymphoma and this approval fills an unmet medical need for these patients," said Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "We are committed to continuing to expedite the development and review of this type of targeted therapy that offers meaningful treatments for patients."

Mogamulizumab-kpkc is a monoclonal antibody that binds to a protein (called CC chemokine receptor type 4 or CCR4) found on some cancer cells. The approval was based on a clinical trial of 372 patients with relapsed MF or SS who received either mogamulizumab-kpkc or vorinostat. Progression-free survival was longer for patients taking mogamulizumab-kpkc (median 7.6 months) compared to patients taking vorinostat (median 3.1 months).

The most common side effects of treatment with mogamulizumab-kpkc included rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.

Serious warnings of treatment with mogamulizumab-kpkc include the risk of dermatologic toxicity, infusion reactions, infections, autoimmune problems, and complications of stem cell transplantation that uses donor stem cells after treatment with the drug.

The FDA granted this application Priority Review and Breakthrough Therapy designation. Mogamulizumab-kpkc also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Wednesday, August 1, 2018

The FDA recently approved iobenguane I 131 injection for intravenous use for the treatment of adults and adolescents age 12 and older with rare tumors of the adrenal gland (pheochromocytoma or paraganglioma) that cannot be surgically removed, have spread beyond the original tumor site and require systemic anticancer therapy. This is the first FDA-approved drug for this use.

"Many patients with these ultra-rare cancers can be treated with surgery or local therapies, but there are no effective systemic treatments for patients who experience tumor-related symptoms such as high blood pressure," said Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Patients will now have an approved therapy that has been shown to decrease the need for blood pressure medication and reduce tumor size in some patients."

Pheochromocytomas are rare tumors of the adrenal glands. These glands are located right above the kidneys and make hormones including stress hormones called epinephrines and norepinephrines. Pheochromocytomas increase the production of these hormones, leading to hypertension and symptoms such as headaches, irritability, sweating, rapid heart rate, nausea, vomiting, weight loss, weakness, chest pain, or anxiety. When this type of tumor occurs outside the adrenal gland, it is called a paraganglioma.

The efficacy of iobenguane I 131 was shown in a single-arm, open-label, clinical trial in 68 patients that measured the number of patients who experienced a 50 percent or greater reduction of all antihypertensive medications lasting for at least 6 months. This endpoint was supported by the secondary endpoint, overall tumor response measured by traditional imaging criteria. The study met the primary endpoint, with 17 (25%) of the 68 evaluable patients experiencing a 50 percent or greater reduction of all antihypertensive medication for at least 6 months. Overall tumor response was achieved in 15 (22%) of the patients studied.

The most common severe side effects reported by patients receiving iobenguane I 131 in clinical trials included lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized ratio (a laboratory test which measures blood clotting), nausea, dizziness, hypertension, and vomiting.

As it is a radioactive therapeutic agent, iobenguane I 131 includes a warning about radiation exposure to patients and family members, which should be minimized while the patient is receiving iobenguane I 131. The risk of radiation exposure is greater in pediatric patients. Other warnings and precautions include a risk of myelosuppression, underactive thyroid, elevations in blood pressure, renal failure or kidney injury, and pneumonitis. Myelodysplastic syndrome and acute leukemias, which are cancers of the blood and bone marrow, were observed in patients who received A iobenguane I 131, and the magnitude of this risk will continue to be studied. The therapy can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception after receiving iobenguane I 131. Radiation exposure associated with iobenguane I 131 may cause infertility in males and females.

The FDA granted this application Fast Track, Breakthrough Therapy, and Priority Review designations. Iobenguane I 131 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.