抗VEGF受容体抗体サイラムザによる転移性EGFR 変異陽性NSCLC 1 次療法

FDA の腫瘍薬諮問委員会(ODAC；Oncology DrugAdvisory Committee)が、治療歴の無い転移性EGFR 変異陽性非小細胞肺癌(NSCLC)患者に対するサイラムザ (一般名：ラムシルマブ) とエルロチニブ の併用療法を評価した第3 相RELAY 試験結果を基に申請したsBLA を審議し、採決の結果6：5 で承認勧告を採択した。RELAY 試験では、VEGF 受容体2 拮抗薬ラムシルマブ と、グローバルに承認済みのEGFR 標的とするチロシンキナーゼ阻害剤(TKI) エルロチニブの併用療法が、エルロチニブ単剤療法と比較して、無増悪生存期間(PFS)を統計的に有意に、かつ臨床的にも意味のある改善を証明した。しかし、奏効率(ORR)、奏効期間(DOR)には有意差が認められずネガティブな結論であった。
未治療の転移性EGFR陽性NSCLC患者に対するラムシルマブとエルロチニブの併用療法のベネフィット・リスクプロファイル？との問いに、諮問委員の採決の結果6：5 で辛うじて承認勧告が採択された。

RK融合遺伝子陽性がん患者に対してlarotrectinibが３年を超えて高い奏効率を維持

Sep 28, 2019　　Bayer, TRK inhibitor, Multiple organ cancer

Updated analysis for larotrectinib confirms high response rate and durable responses over three years in children and adults with TRK fusion cancer

• larotrectinibはTRK融合遺伝子陽性がん患者で３年を超える高い奏効率と持続効果が最新の解析で確認された。

バイエルのTRK阻害薬ビトラクヴィががん種を問わない幅広い適応症で欧州承認を取得

Vitrakvi® (larotrectinib) receives first tumor-agnostic approval in EU

• バイエルのTRK阻害薬ビトラクヴィが「遺伝子変異（NTRK融合遺伝子）を有する固形がん」という幅広い適応症で欧州承認を取得した。欧州委員会（EC）が発生臓器を問わない幅広い効能で抗がん剤を承認するのは初めて。米国では昨年（2018年）11月に承認されている。売上高1000億円に達すると予想する。

ファーマセットLibrary項目へのリンク　Bayer, TRK inhibitor

ラロトレクチニブの米国におけるローリング承認申請が完了

Bayer announces completion of rolling submission of New Drug Application in the U.S. for larotrectinib for the treatment of TRK fusion cancer

March 26, 2018 » Bayer, TRK fusion cancer

• バイエルはトロポミオシン受容体キナーゼ（TRK）融合遺伝子を有するがんに対する治療薬ラロトレクチニブの米国におけるローリング承認申請を完了した。TRKのシグナル伝達が制御できなくなり腫瘍増殖をもたらすTRK 融合遺伝子はさまざまな腫瘍に見られる遺伝子変化である。

トロポミオシン受容体キナーゼ（TRK）融合遺伝子を有する癌の治療薬

Bayer announces initiation of rolling submission of new drug application in the U.S. for larotrectinib for the treatment of TRK fusion cancers
December 20, 2017

• バイエルはトロポミオシン受容体キナーゼ（TRK）融合遺伝子を有する癌の治療薬として開発中のラロトレクチニブの米国におけるローリング申請を開始した。

Berlin, December 20, 2017 – Bayer today announced that its collaboration partner Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company based in Stamford, CT, has initiated the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for larotrectinib. The NDA is being submitted for the treatment of unresectable or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments. Bayer and Loxo Oncology are jointly developing larotrectinib, an investigational compound being studied globally for the treatment of patients with cancers harboring tropomyosin receptor kinase (TRK) gene fusions, which are genetic alterations present across a wide range of tumors resulting in uncontrolled TRK signaling and tumor growth. Loxo Oncology expects to complete the NDA submission in early 2018.

“The initiation of the rolling submission in the U.S. by Loxo Oncology is an important milestone, as it brings us one step closer to potentially being able to offer a much needed new treatment option for patients with TRK fusion cancers in the near future,” said Robert LaCaze, Member of the Executive Committee at Bayer AG’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit.

About larotrectinib (LOXO-101)

Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated an 80 percent investigator-assessed overall response rate (ORR) and a 75 percent independently-reviewed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

In November 2017, Loxo Oncology and Bayer entered into an exclusive global collaboration for the development and commercialization of larotrectinib and LOXO-195, a next-generation TRK inhibitor. Loxo Oncology leads worldwide development and U.S. regulatory activities. Bayer leads ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

About TRK fusion cancer

TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

Link » Bayer, TRK fusion