Abstract：
Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov).
Durvalumab is a treatment that helps the body\'s immune system to identify and attack cancer cells by binding to a protein called PD-L1. Studies show that durvalumab lowers the risk of cancer growing or spreading, and prolongs survival, when administered after chemotherapy and radiation therapy (‘chemoradiotherapy’) in patients with a type of lung cancer called stage III non-small-cell lung cancer (NSCLC) for whom surgery is not an option.Two antibody treatments have been developed that may help a patient\'s immune system to identify and attack cancer cells. Oleclumab binds to a protein on cancer cells called CD73, which prevents the production of adenosine, a chemical that obstructs the immune system from attacking the cancer. Monalizumab binds to NKG2A, a protein on immune cells that inhibits their ability to destroy cancer cells. Early studies suggest that combining either of these treatments with durvalumab may be better than durvalumab alone for slowing the growth and spread of cancer in patients with NSCLC.PACIFIC-9 is a study that aims to recruit approximately 999 patients with stage III NSCLC for whom surgery is not an option and who have completed chemoradiotherapy without the cancer growing or spreading. Patients will be randomly assigned in equal numbers to receive up to a year of treatment with durvalumab plus oleclumab, durvalumab plus monalizumab or durvalumab plus placebo. The primary measure of efficacy is the length of time that patients remain alive without the cancer growing or spreading for each combination versus durvalumab plus placebo.
Durvalumab is a treatment that helps the body\'s immune system to identify and attack cancer cells by binding to a protein called PD-L1. Studies show that durvalumab lowers the risk of cancer growing or spreading, and prolongs survival, when administered after chemotherapy and radiation therapy (‘chemoradiotherapy’) in patients with a type of lung cancer called stage III non-small-cell lung cancer (NSCLC) for whom surgery is not an option.Two antibody treatments have been developed that may help a patient\'s immune system to identify and attack cancer cells. Oleclumab binds to a protein on cancer cells called CD73, which prevents the production of adenosine, a chemical that obstructs the immune system from attacking the cancer. Monalizumab binds to NKG2A, a protein on immune cells that inhibits their ability to destroy cancer cells. Early studies suggest that combining either of these treatments with durvalumab may be better than durvalumab alone for slowing the growth and spread of cancer in patients with NSCLC.PACIFIC-9 is a study that aims to recruit approximately 999 patients with stage III NSCLC for whom surgery is not an option and who have completed chemoradiotherapy without the cancer growing or spreading. Patients will be randomly assigned in equal numbers to receive up to a year of treatment with durvalumab plus oleclumab, durvalumab plus monalizumab or durvalumab plus placebo. The primary measure of efficacy is the length of time that patients remain alive without the cancer growing or spreading for each combination versus durvalumab plus placebo.
摘要：
来自PACIFICIII期试验的证据建立了Durvalumab，一种针对PD-L1的单克隆抗体（mAb），在同步放化疗（cCRT）后作为不可切除患者的全球护理标准，III期非小细胞肺癌（NSCLC）。PACIFIC方案取得的成果仍未得到满足。将Durvalumab与其他免疫疗法结合使用可能会进一步改善结果。两种这样的免疫疗法包括orolumab，一种针对CD73和monalizumab的单克隆抗体，一种靶向NKG2A的单克隆抗体。两种药物在早期试验中均显示出抗肿瘤活性。PACIFIC-9（NCT05221840）是一种国际，双盲,随机化，安慰剂对照,III期试验，比较durvalumab联合orolumab或monalizumab与durvalumab联合安慰剂治疗不可切除的患者，III期NSCLC，cCRT后无疾病进展。临床试验注册：NCT05221840（ClinicalTrials.gov）。
Durvalumab是一种通过与称为PD-L1的蛋白质结合来帮助人体免疫系统识别和攻击癌细胞的治疗方法。研究表明，durvalumab可以降低癌症生长或扩散的风险，延长生存期，当在化疗和放疗('放化疗')后对一种称为III期非小细胞肺癌(NSCLC)的肺癌患者进行治疗时,手术不是一种选择.已经开发了两种抗体治疗方法，可以帮助患者的免疫系统识别和攻击癌细胞。Oleclumab与癌细胞上的一种叫做CD73的蛋白质结合，阻止腺苷的产生，一种阻止免疫系统攻击癌症的化学物质。Monalizumab与NKG2A结合，免疫细胞上的一种蛋白质，抑制它们破坏癌细胞的能力。早期研究表明，在NSCLC患者中，将这些治疗方法与durvalumab结合使用可能比单独使用durvalumab更好地减缓癌症的生长和扩散。PACIFIC-9是一项旨在招募约999名III期NSCLC患者的研究，这些患者不能选择手术，并且已经完成了放化疗而没有癌症生长或扩散。患者将被随机分配相同的数量，以接受durvalumab加oleclumab长达一年的治疗，durvalumab联合monalizumab或durvalumab联合安慰剂.疗效的主要衡量标准是每种组合与durvalumab加安慰剂相比，患者在没有癌症生长或扩散的情况下存活的时间长度。
Durvalumab是一种通过与称为PD-L1的蛋白质结合来帮助人体免疫系统识别和攻击癌细胞的治疗方法。研究表明，durvalumab可以降低癌症生长或扩散的风险，延长生存期，当在化疗和放疗('放化疗')后对一种称为III期非小细胞肺癌(NSCLC)的肺癌患者进行治疗时,手术不是一种选择.已经开发了两种抗体治疗方法，可以帮助患者的免疫系统识别和攻击癌细胞。Oleclumab与癌细胞上的一种叫做CD73的蛋白质结合，阻止腺苷的产生，一种阻止免疫系统攻击癌症的化学物质。Monalizumab与NKG2A结合，免疫细胞上的一种蛋白质，抑制它们破坏癌细胞的能力。早期研究表明，在NSCLC患者中，将这些治疗方法与durvalumab结合使用可能比单独使用durvalumab更好地减缓癌症的生长和扩散。PACIFIC-9是一项旨在招募约999名III期NSCLC患者的研究，这些患者不能选择手术，并且已经完成了放化疗而没有癌症生长或扩散。患者将被随机分配相同的数量，以接受durvalumab加oleclumab长达一年的治疗，durvalumab联合monalizumab或durvalumab联合安慰剂.疗效的主要衡量标准是每种组合与durvalumab加安慰剂相比，患者在没有癌症生长或扩散的情况下存活的时间长度。
