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药企合作 PD-1

2月5日,德国默克与GSK宣布双方达成全球战略合作联盟,联合开发靶向PD-L1/TGF-β的双功能融合蛋白类肿瘤免疫疗法M7824(bintrafusp alfa)。 



截至目前,有10种以上不同癌症类型的近700例患者在I期研究中接受了M7824 的治疗。M7824在晚期NSCLC、人HPV病毒相关癌症、胆道癌、胃癌等多种难治性癌症中显示出了令人兴奋的临床数据。ASCO2018大会上公布的M7824的两项早期临床数据也成为大家关注的焦点。




默克医疗健康业务CEO Belén Garijo表示:“M7824有望给难治性癌症患者带来新的生机。GSK对肿瘤领域有强烈的投入意愿,是一个理想的合作伙伴。我们双方也有不同的优势可以互补合作,成为这类新型肿瘤免疫疗法的领军企业。我们期待全面发掘M7824 对一系列癌症的治疗潜力。”

GSK首席科学官&全球研发总裁Hal Barron表示:“尽管肿瘤治疗取得了很大的进步,仍有很多难治性癌症患者无法从当前的免疫疗法中获益。M7824是融合两种不同生物学功能的蛋白药物,在某些癌症患者中也显示出了令人兴奋的治疗效果。我很期待这种首创的免疫疗法能够改变癌症患者的命运。”



On February 5, Merck and GSK announced that they have reached a global strategic cooperation alliance to jointly develop a bifunctional fusion protein tumor immunotherapy M7824 (bintrafusp alfa) targeting PD-L1/TGF-β.

According to the agreement, Merck can receive 300 million euros in down payment from GSK, 500 million euros in R & D mileage based on lung cancer clinical data, and 2.9 billion euros in marketing and commercial mileage in the future, with the total amount of the whole transaction reaching 3.7 billion euros.Both parties will jointly be responsible for the future clinical development and commercial promotion of M7824 worldwide, and the resulting costs and profits will be shared equally by both parties.

M7824 is a bifunctional fusion protein, one end is able to recognize the antibody structure (Y) that binds to PD-L1, and the other end is a TGF-β receptor type II fusion protein (Trap) that can bind to TGF-β, which can block both PD-L1 and TGF-β signaling pathways, relieve the inhibitory state of the immune system, and improve the killing effect of the immune system on cancer cells.

Up to now, nearly 700 patients with more than 10 different cancer types have been treated with M7824 in phase I studies.M7824 in advanced NSCLC.Human HPV virus-associated cancer.Biliary tract cancer.Gastric cancer and other refractory cancers show exciting clinical data.The two early clinical data of M7824 presented at ASCO 2018 have also become the focus of attention.

1) patients with stage IV NSCLC who had received platinum-based chemotherapy but not PD-1 inhibitors received 500 mg (n = 40) and 1200 mg (n = 40) of M7824 monotherapy, respectively.The data showed that the ORR of patients in the 1200 mg high dose group was 27.5%, in which PD-L1 positive (PD-L1> 1%) patients achieved ORR of 40.7% (n = 11/27).Patients with high PD-L1 expression (PD-L1> 80%) have an ORR up to 71.4% (n = 5/7), which is superior to the general response rate of 20% -40% for PD-1 inhibitors.

2) Patients with HPV-related cancer were treated with different doses of M7824, of which 12 were identified to carry HPV infection.For these 12 patients with established HPV-infected tumors, 1 tumor completely disappeared, 4 tumors shrank significantly, and 1 tumor was stable, with an overall response rate of up to 41.7%, which is superior to the response rate of less than 20% in general for PD-1 inhibitors.

M7824 can reduce the side effects of the combination, and since the TGF-β pathway also plays a key role in the development of pulmonary fibrosis, inhibition of the TGF-β pathway can not only improve the efficacy of non-small cell lung cancer, but may also reduce patients with pneumonia and pulmonary fibrosis caused by chemoradiotherapy.In view of the unique mechanism of action of Y-Traps, M7824 is known as a 2nd generation PD-1 inhibitor or an upgraded PD-1 inhibitor, and there are several ongoing clinical studies for refractory cancer, including a phase II study comparing the efficacy and safety of M7824 and Keytruda as single-agent first-line therapy for advanced NSCLC with high expression of PD-L1 in addition to the above-mentioned phase I study.

Belén Garijo, CEO of Merck Healthcare, said: "M7824 is expected to bring new vitality to patients with refractory cancer.GSK has a strong willingness to invest in the field of oncology and is an ideal partner.We also have different strengths to complement each other and become the leader in this new type of cancer immunotherapy. We look forward to fully exploring the therapeutic potential of M7824 for a range of cancers. ”

Hal Barron, GSK's Chief Scientific Officer & Global R&D President, said: "Although cancer therapy has made great progress, there are still many patients with refractory cancer who cannot benefit from current immunotherapy. M7824 is a fusion of two different biological functions. The protein drug has also shown exciting therapeutic effects in some cancer patients. I am looking forward to this pioneering immunotherapy to change the fate of cancer patients.

GSK has just announced the acquisition of Tesaro.The cooperation with Merck also reflects the importance and investment of GSK in the frontier areas of IO therapy, cell therapy, epigenetics, gene editing, etc. It is not uncommon for pharmaceutical giants to establish cooperative alliances or deep-bundling on a drug. MSD revolved around Olapalil in 2017. Lenvatinib and AstraZeneca. Eisai reached a total of 8.5 billion US dollars and 5.755 billion US dollars in cooperation agreements.


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