【原】【囍临门】entrectinib和polatuzumab vedotin申报上市均获优审

FDA grants Priority Review to Roche's personalised medicine entrectinib

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the US Food and Drug Administration (FDA) has accepted the company’s New Drug Applications (NDAs) and granted Priority Review for entrectinib for the treatment of adult and paediatric patients with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive, locally advanced or metastatic solid tumours who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic, ROS1-positive non-small cell lung cancer (NSCLC). These NDAs are based on results from the integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the Phase I/Ib STARTRK-NG study. The FDA is expected to make a decision on approval by 18 August 2019.

entectinib大家比较熟悉，这次申报的数据是基于合并的 1期的ALKA-372-001 、STARTRK-1 和2期的STARTRK-2，以及I/Ib期的STARTRK-NG研究，如下

Entrectinib是口服的、强效的、所有TRK蛋白和ROS1的选择性抑制剂，在颅内也有活性。插个题外话，和已经获批上市的Larotrectinib相比，多了对ROS1的抑制能力：ROS1+ NSCLC的小样本研究中，不管有无脑转移，都带来明显的临床获益

几个合并的研究的设计

基线情况：42%属于≥3L治疗；22%有CNS转移；肉瘤、NSCLC和涎腺分泌性癌(MASC)患者合计超过50%

整体ORR 54.5%，DCR 74.1%，几个患者数较多的类型中，缓解较好的包括NSCLC、乳腺癌和涎腺分泌性癌患者

有无CNS转移的ORR相差不大

几种NTRK基因融合亚型的缓解率比较，NTRK1和NTRK3基因融合的缓解率很接近，由于这几个研究都没有NTRK2融合的患者，所以无法判断该类患者的情况

DOR、PFS和OS分别10.4mo、11.2mo和20.0mo

CNS患者的颅内ORR 54.5%，与全身缓解57.4%十分接近

安全性可控，大多数可以通过剂量调整或者中断解决，只有3.9%引起治疗终止

总结如下

有人非要拿来和Larotrectinib相比：只能说如果不考虑CNS转移的TRK融合的结果是Larotrectinib好，另外说实话across BBB弱，整个临床只有2%CNS转移，而Entrectinib则瞄向了ROS1，谁让人家across BBB牛

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FDA grants priority review to Roche’s polatuzumab vedotin in previously treated aggressive lymphoma

• Diffuse large B-cell lymphoma is an aggressive type of blood cancer that typically becomes harder to treat each time it returns

• Polatuzumab vedotin has shown significant potential to improve outcomes in people living with this disease

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for polatuzumab vedotin in combination with bendamustine plus Rituxan® (rituximab) (BR) for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The FDA is expected to make a decision on approval by 19 August 2019.

• Polatuzumab vedotin(pola)是靶向表达在FL和DLBCL等B细胞淋巴瘤表面的CD79b的ADC药物，附：靶点的合理性：CD79 has the appropriate expression pattern, being expressed only on B cells and in most NHLs

• 先前Pola联合利 苯达莫司汀+妥昔单抗（BR）在针对先前重度治疗的R/R的FL和DLBCL的1b/2期单臂研究中显示出可控的安全性和令人满意的ORR（G为obinutuzumab）

https://learningcenter./eha/2017/22nd/181755/matthew.matasar.polatuzumab.vedotin.plus.bendamustine.and.rituximab.or.html

接受6个疗程，主要终点治疗完成后6-8周IRC测定的PET-CR

可以看出，FL两组接受的中位疗程数接近，DLBCL中两组接受的中位疗程数有差别，BR组完成完整疗程的少于Pola-BR组

Pola-BR组sAE率更高，最常见的是感染和FN

Pola-BR中的外周血中性粒细胞减少多数为1-2级且可逆，两组5级AE接近：11% vs 12

FL中，两组PET-CR和ORR接近，PFS无显著差异

DLBCL中，Pola-BR组的PET-CR显著提高(下图左)

Pola-BR组的PFS和OS都得到明显延长

所以这次申报是基于DLBCL的结果

愿景如此