7月25、2021： ギリアド社（ナスダック：GILD）のカイトは本日、FDAがTecartusTM（brexucabtagene autoleucel、以前はKTE-X19）を承認したことを発表しました。 キメラ抗原受容体CART細胞療法 for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, accelerated approval (MCL). The FDA granted priority review and breakthrough therapy designation to this one-time therapy, which was based on the results of ZUMA-2, a single-arm, open-label study in which 87 percent of patients responded to a single infusion of Tecartus, with 62 percent achieving a complete response (CR). 18% of patients who were evaluated for safety had サイトカイン放出症候群 (CRS) of Grade 3 or higher, and 37% had neurologic toxicities of Grade 3 or higher.
“Despite promising advances, there are still significant gaps in treatment for MCL patients who progress after initial therapy,” said Michael Wang, MD, ZUMA-2 Lead Investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center. “Many patients have high-risk disease, which means they are more likely to progress despite treatment. “Tecartus is the first cell therapy available to people with relapsed or refractory MCL. It has an impressive response rate of nearly 90% and early clinical evidence suggests that remissions may last through later lines of therapy. This makes it an important choice for these patients.”
「カイトは CAR T療法 to patients with haematological cancers,” said Christi Shaw, Kite’s Chief Executive Officer. “I would like to express my gratitude to the patient study participants, caregivers, clinical researchers, regulators, and dedicated Kite colleagues who contributed to this approval, and we look forward to working with the リンパ腫 community to bring this potentially transformative therapy to patients with relapsed or refractory MCL.”
Tecartus’ product label includes a boxed warning about the risks of CRS and neurologic toxicities. The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Tecartus, which has been combined with the REMS for Yescarta® (axicabtagene ciloleucel). The REMS programme will inform and educate healthcare professionals about the risks associated with Tecartus therapy, and training and certification in the REMS programme will be a requirement for centres offering Tecartus therapy to receive final authorization.
MCLは珍しいタイプです 非ホジキンリンパ腫 （NHL）リンパ節の「マントルゾーン」の細胞から発生し、主に60歳以上の男性に発症します。再発後、MCLは非常に攻撃的であり、多くの患者が治療後に進行します。
The Lymphoma Research Foundation’s Chief Executive Officer, Meghan Gutierrez, said, “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.” “Researchers have made significant progress in our understanding of this disease over the last decade, and we’ve seen an increase in patient clinical trials, which we hope will continue to improve treatment strategies and options for people with mantle cell lymphoma. Today’s news builds on that progress and gives mantle cell patients and their families reason to be hopeful.”
Kite’s commercial manufacturing facility in El Segundo, California, will produce Tecartus. Kite achieved a 96 percent manufacturing success rate in the ZUMA-2 trial, with a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Patients with advanced disease, who are severely ill and at risk of rapid progression, require manufacturing speed in particular.
KiteKonnect®、Kiteの商品化された治療プロセス全体を通じて情報と支援を提供する統合テクノロジープラットフォーム CART療法, including courier tracking for shipments and manufacturing status updates, is available to patients whose healthcare professionals have prescribed Tecartus therapy. Kite Konnect is a support system for patients who are receiving Yescarta or Tecartus, as well as information for the healthcare teams who are supporting them.
KTE-X19は現在、欧州連合で評価されており、欧州医薬品庁は、再発または難治性のMCLに対してPriority Medicines（PRIME）の指定を与えています。
Tecartus試験結果
The approval of Tecartus is based on results from the ongoing ZUMA-2 pivotal trial, which is a single arm, open-label study. 74 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, anti-CD20 antibody treatment, or a Bruton tyrosine kinase inhibitor were enrolled in the trial (ibrutinib or acalabrutinib). The primary endpoint was the objective response rate (ORR), which was defined as the combined rate of CR and partial responses as judged by an Independent Radiologic Review Committee according to the Lugano Classification (2014). (IRRC).
この研究では、87％の患者（有効性分析で評価可能なn = 60）が62回のTecartus注入に反応し、XNUMX％が完全な反応を達成しました。 フォローアップは、すべての患者の最初の客観的疾患反応から少なくともXNUMXか月後でした。 反応時間の中央値はまだ決定されていません。
In the experiment, 18% of patients (n=82 evaluable for safety) had Grade 3 or higher CRS, while 37% of patients had neurologic problems. Anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unclear, pneumonia, hypocalcemia, and lymphopenia were the most prevalent Grade 3 or higher adverse effects (10%). With a Risk Evaluation and Mitigation Strategy, the FDA approved Tecartus (REMS). The Yescarta (axicabtagene ciloleucel) and Tecartus (ブレクスカブタゲン オートロイセル) REMS Program has been integrated with the Tecartus REMS and is now known as the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program”
Tecartusについて
Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP™ 循環リンパ芽球が一般的な特徴である特定のB細胞悪性腫瘍に必要なステップであるT細胞濃縮を含む製造プロセス。 MCLに加えて、Tecartusは現在、急性リンパ芽球性白血病（ALL）および 慢性リンパ性白血病 (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.
Tecartusの適応症
Tecartus は、再発性または難治性のマントル細胞リンパ腫 (MCL) の成人患者の治療を適応とする CD19 指向の遺伝子組み換え自己 T 細胞免疫療法です。
この適応症は、全体的な奏効率と奏効の持続性に基づいて迅速承認の下で承認されます。 この適応症の継続的な承認は、確認試験における臨床的利益の検証と説明を条件とする場合があります。
