AstraZeneca CEO Pascal Soriot has agreed to take the helm at Teva

MYSTIC trial (P3 durvalumab + tremelimumab in NSCLC) 결과 발표를 앞두고, AZ CEO Pascal Soriot 가 Teva 로 옮긴다는 이 기사는 무엇인가.

이미 MYSTIC trial 을 놓고 지난주에 로이터블룸버그에서 한 바탕 난리를 치는 기사가 나왔는데, 일단 현재 부정적인 예상이 우세한 가운데, CEO 의 교체는 쐐기골 같은 느낌이다.

한 차례 NSCLC 에서 실패하여 왕좌의 자리를 넘겨준 BMS 의 케이스와 비교가 되는 것은 어쩔 수 없는데,

한편으로 안타까운 점은 화이자의 117B USD 의 인수제안을 거부한 것이 결론적으로 성공적인가 아닌가가 그분들에게는 중요하겠지만, 

나름 과학을 하는 입장에서는 씁쓸한 소식이긴하다.

우선은 공식적인 데이터가 나올때 까지 무슨 일이 벌어질지 모르니…

출처

FDA grants accelerated approval to avelumab for urothelial carcinoma

Merck KGaA 와 Pfizer 가 만든 avelumab 이 MCC 에 이어 두번째로 urothelial carcinoma 에서 승인을 받았다. 

Roche 와 마찬가지로 accelerated approval 을 받았고, 오늘 OS 에 도달하지 못한 임상3상 결과를 발표한 Roche 와 함께, 또한 올해 승인받은 BMS 의 Opdivo 와, AZ 의 Imfinzi 와 함꼐, 이 암종에서 경쟁할 것으로 보인다. (타이밍이 참…)

링크

자세한기사링크

FDA grants atezolizumab accelerated approval as frontline therapy in advanced bladder cancer

Atezolizumab 이 작년 bladder cancer 에서 런칭한 이후 1년만에 first line therapy 로 업그레이드 되면서, 이 암종에서 standard of care 가 될 것으로 보인다.

1. Patients with advanced bladder cancer who are not eligible for standard cisplatin chemo

2. Based on data from the single-arm phase II IMvigor210 trial

3. ORR 23.5%, CR 6.7%

http://www.onclive.com/web-exclusives/fda-approves-frontline-atezolizumab-for-some-bladder-cancer-patients

http://www.roche.com/media/store/releases/med-cor-2017-04-18.htm

FDA Grants Approval for BAVENCIO® (avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell Carcinoma

Pfizer 가 4번째로 PD-1/PD-L1 약물을 시장에 발매했다. AZ 가 될 줄 알았건만,

링크

ORR 33%, CR 11%, PR 22%

 

이로써, PD-1 inhibitor 2개, PD-L1 inhibitor 2개가 되었고, 기존 약물들과의 경쟁은 어떻게 될지가 궁금하다.

누가 또 아는가, 갑자기 pembrolizumab 이 그랬던 것 처럼, 단숨에 치고 올라올지,,,

기존 Pfizer oncology pipeline 을 보면 어떤 약물과 combo-trial 을 갈지는 당장 감이 오질 않는다. 찾아보기도 귀찮고,,

일단 NSCLC, gastric, ovarian 등 임상 진행 중인 결과가 기존 약물과 직접적인 경쟁이 될 필드이기도 하니 좋은 징조인 것 같다.

하루빨리 durvalumab 도 가세하길…

 

Atezolizumab vs docetaxel in patients with previously treated NSCLC (OAK): a phase 3, open-label, multicentre randomised controlled trial

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.

Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara, and OAK Study Group.

BACKGROUND:Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.

METHODS:We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients had received one to two previous cytotoxic chemotherapy regimens (one or more platinum based combination therapies) for stage IIIB or IV non-small-cell lung cancer. Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel, CD137 agonists, anti-CTLA4, or therapies targeting the PD-L1 and PD-1 pathway were excluded. Patients were randomly assigned (1:1) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m(2) every 3 weeks by permuted block randomisation (block size of eight) via an interactive voice or web response system. Coprimary endpoints were overall survival in the intention-to-treat (ITT) and PD-L1-expression population TC1/2/3 or IC1/2/3 (≥1% PD-L1 on tumour cells or tumour-infiltrating immune cells). The primary efficacy analysis was done in the first 850 of 1225 enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02008227.

FINDINGS:Between March 11, 2014, and April 29, 2015, 1225 patients were recruited. In the primary population, 425 patients were randomly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel. Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression populations. In the ITT population, overall survival was improved with atezolizumab compared with docetaxel (median overall survival was 13·8 months [95% CI 11·8-15·7] vs 9·6 months [8·6-11·2]; hazard ratio [HR] 0·73 [95% CI 0·62-0·87], p=0·0003). Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab (n=241) compared with docetaxel (n=222; median overall survival was 15·7 months [95% CI 12·6-18·0] with atezolizumab vs 10·3 months [8·8-12·0] with docetaxel; HR 0·74 [95% CI 0·58-0·93]; p=0·0102). Patients in the PD-L1 low or undetectable subgroup (TC0 and IC0) also had improved survival with atezolizumab (median overall survival 12·6 months vs 8·9 months; HR 0·75 [95% CI 0·59-0·96]). Overall survival improvement was similar in patients with squamous (HR 0·73 [95% CI 0·54-0·98]; n=112 in the atezolizumab group and n=110 in the docetaxel group) or non-squamous (0·73 [0·60-0·89]; n=313 and n=315) histology. Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab (90 [15%] of 609 patients) versus docetaxel (247 [43%] of 578 patients). One treatment-related death from a respiratory tract infection was reported in the docetaxel group.

INTERPRETATION:To our knowledge, OAK is the first randomised phase 3 study to report results of a PD-L1-targeted therapy, with atezolizumab treatment resulting in a clinically relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer, regardless of PD-L1 expression or histology, with a favourable safety profile.

FUNDING:F. Hoffmann-La Roche Ltd, Genentech, Inc.

Lancet, 2017 vol. 389 (10066) pp. 255-265.

http://linkinghub.elsevier.com/retrieve/pii/S014067361632517X

스크린샷 2017-03-23 오전 12.45.04

스크린샷 2017-03-23 오전 12.45.32

스크린샷 2017-03-23 오전 12.46.33TC1/2/3 or IC1/2/3: PD-L1 >= 1%
TC2/3 or IC2/3: 5%
TC3: 50% Tumor PD-L1
IC3: 10% Immune cell PD-L1
TC0 and IC0: PD-L1 < 1%

All images are from 여기.