FDA News: September 2020

TOP - September 2020 Vol 13, No 5 - FDA Updates

This section provides a brief overview of new cancer drugs or new indications approved by the FDA between June 30, 2020, and July 24, 2020.

FDA Approves Tecartus for the Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma

On July 24, 2020, the FDA approved brexucabtagene autoleucel (Tecartus; Kite Pharma), a chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with mantle-cell lymphoma (MCL) who have not responded to, or who have relapsed following, other types of treatment. Tecartus is an autologous CAR T-cell therapy that targets the CD19 protein on the surface of cancer cells. The FDA granted Tecartus a priority review and an orphan drug designation.

“Tremendous progress has been made in the discovery of new therapies for debilitating diseases that are difficult to treat. This approval is yet another example of customized treatments that use a patient’s own immune system to help fight cancer, while using a scientific advance in this promising new area of medicine. We’re seeing continued advances in the field of gene therapy and remain committed to supporting innovation in this promising new area of medicine,” said Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research.

The FDA approval of brexucabtagene autoleucel was based on results of the ongoing, pivotal, single-arm ZUMA-2 clinical trial that enrolled 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor.

The primary efficacy outcome measure in the trial was objective response rate (ORR) as assessed by an independent review committee. Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of 6 months, the ORR was 87%, with a complete remission rate of 62%. The estimated median duration of response was not reached after a median follow-up time for duration of response of 8.6 months.

The most common (≥10%) grade 3 or higher adverse events associated with brexucabtagene autoleucel were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

The prescribing information for Tecartus also carries a boxed warning that outlines risks for cytokine release syndrome and neurotoxicity associated with CAR T-cell therapy.

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Inqovi First Oral Hypomethylating Agent Approved for Intermediate- or High-Risk MDS

On July 7, 2020, the FDA approved decitabine plus cedazuridine (Inqovi; Astex Pharmaceuticals/Taiho Oncology) for the treatment of adults with intermediate- or high-risk myelodysplastic syndromes (MDS), including patients with chronic myelomonocytic leukemia (CMML). Inqovi is an orally administered fixed-dose combination of the hypomethylating agent decitabine plus the cytidine deaminase inhibitor cedazuridine. The FDA granted Inqovi a priority review and an orphan drug designation.

The FDA approval of decitabine plus cedazuridine was based on data from the phase 3 ASCERTAIN clinical trial, as well as on supporting data from phase 1 and phase 2 clinical trials evaluating this regimen.

The ASCERTAIN study compared the efficacy and safety of 5-day administration of oral decitabine plus cedazuridine versus intravenous (IV) decitabine. Results showed similar drug concentrations and safety profiles between the 2 treatments. Additionally, approximately 50% of the patients who were formerly dependent on transfusions were able to no longer require transfusions during an 8-week period.

Guillermo Garcia-Manero, MD, Professor and Chief of Section of Myelodysplastic Syndromes, Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX, and lead investigator of the ASCERTAIN trial, said, “Intravenous or subcutaneous administered hypomethylating agents have been the cornerstone for the treatment of patients with MDS and CMML since the mid-2000s. The FDA’s approval of Inqovi builds on the proved therapeutic utility of hypomethylating agents in these diseases and offers a new orally administered option that offers patients an alternative to 5 consecutive days of IV infusions every month during a treatment period that can extend to several months.”

The most common (≥20%) adverse reactions associated with decitabine plus cedazuridine were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increases. The most common (≥50%) grade 3 or 4 laboratory abnormalities were decreases in leukocytes, platelet count, neutrophil count, and hemoglobin levels.

Serious adverse reactions (>5%) associated with the use of decitabine plus cedazuridine included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%).

Adverse events leading to death included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and 1 case each of cerebral hemorrhage and sudden death.

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Bavencio Approved as First-Line Maintenance Therapy for Patients with Bladder Cancer

On June 30, 2020, the FDA approved avelumab (Bavencio; Pfizer) for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. This approval was based on results of the randomized, multicenter, open-label, phase 3 JAVELIN Bladder clinical trial, which enrolled 700 patients with unresectable, locally advanced, or metastatic urothelial carcinoma that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy.

Patients were randomized to avelumab given intravenously every 2 weeks plus best supportive care (BSC) or BSC alone. The primary end points of the trial were overall survival (OS) in all patients and in patients with PD-L1–positive disease. Results showed that the addition of avelumab to BSC led to a 7.1-month improvement in OS in all patients (21.4 months vs 14.3 months; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.56-0.86; P = .001). Among patients with PD-L1–positive tumors (51%), the HR for OS was 0.56 (95% CI, 0.40-0.79; P <.001).

“With median OS of more than 21 months measured from randomization, the longest OS in a phase 3 trial in advanced urothelial carcinoma, the JAVELIN Bladder 100 regimen with avelumab as a first-line switch maintenance treatment has the potential to become a new standard of care based on its proven ability to reinforce the benefit (response or stable disease) of induction chemotherapy and extend the lives of patients with this devastating disease,” said Petros Grivas, MD, PhD, Clinical Director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, who was one of the principal investigators in the trial.

The most common (>20%) adverse events were fatigue, musculoskeletal pain, urinary tract infection, and rash. In total, 28% of patients treated with avelumab experienced a serious adverse event, the most common of which included urinary tract infection (6.1%), pain (3.2%), acute kidney injury (1.7%), hematuria (1.5%), sepsis (1.2%), and infusion-related reaction (1.2%).

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Last modified: July 22, 2021