Abstract：
Patients with early-stage triple-negative breast cancer (TNBC) with residual invasive disease after neoadjuvant therapy have a high risk of recurrence even with neoadjuvant and adjuvant treatment with pembrolizumab. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with pre-treated metastatic TNBC. Moreover, preclinical data suggest that topoisomerase I inhibitors may enhance the effects of immune checkpoint inhibitors through activation of the cGAS-STING pathway. Here we describe the international randomized phase III AFT-65/ASCENT-05/OptimICE-RD trial, which evaluates the efficacy and safety of sacituzumab govitecan plus pembrolizumab versus treatment of physician\'s choice (pembrolizumab ± capecitabine) among patients with early-stage TNBC with residual invasive disease after neoadjuvant therapy.Clinical Trial Registration: NCT05633654 (ClinicalTrials.gov)Other Study ID Number(s): Gilead Study ID: GS-US-595-6184Registration date: 1 December 2022Study start date: 12 December 2022Recruitment status: Recruiting.
AFT-65/ASCENT-05/OptimICE-RD is an ongoing clinical trial that is testing a new treatment combination for patients with stage II or III triple-negative breast cancer (TNBC). Stage II–III means the cancer is confined to the breast and/or nearby lymph nodes and can be surgically removed. However, there remains a risk that the cancer could recur after surgery. To reduce this risk, patients with stage II–III TNBC receive anti-cancer medication before and after surgery. For some patients, receipt of anti-cancer medication before surgery produces a pathologic complete response (pCR), meaning there is no observable cancer left behind at surgery. Patients with a pCR have a lower risk of recurrence than patients with residual disease.The AFT-65/ASCENT-05/OptimICE-RD trial includes people with stage II-III TNBC who have residual cancer after completing their course of pre-surgery anti-cancer medication. All participants have any remaining cancer in their breast and/or lymph nodes removed surgically, after which they are randomly assigned to receive one of two treatments. The experimental therapy consists of pembrolizumab along with a medication called sacituzumab govitecan, which kills cancer cells directly and may strengthen the anti-cancer immune response. Pembrolizumab strengthens the anti-cancer immune response, so the hypothesis of this trial is that the two medications will be more effective together. The control therapy consists of pembrolizumab, alone or in combination with a chemotherapy medication called capecitabine, which is the current standard of care. To study the effectiveness of each treatment, the researchers are following up with all participants to learn if and when their breast cancer returns.
AFT-65/ASCENT-05/OptimICE-RD is an ongoing clinical trial that is testing a new treatment combination for patients with stage II or III triple-negative breast cancer (TNBC). Stage II–III means the cancer is confined to the breast and/or nearby lymph nodes and can be surgically removed. However, there remains a risk that the cancer could recur after surgery. To reduce this risk, patients with stage II–III TNBC receive anti-cancer medication before and after surgery. For some patients, receipt of anti-cancer medication before surgery produces a pathologic complete response (pCR), meaning there is no observable cancer left behind at surgery. Patients with a pCR have a lower risk of recurrence than patients with residual disease.The AFT-65/ASCENT-05/OptimICE-RD trial includes people with stage II-III TNBC who have residual cancer after completing their course of pre-surgery anti-cancer medication. All participants have any remaining cancer in their breast and/or lymph nodes removed surgically, after which they are randomly assigned to receive one of two treatments. The experimental therapy consists of pembrolizumab along with a medication called sacituzumab govitecan, which kills cancer cells directly and may strengthen the anti-cancer immune response. Pembrolizumab strengthens the anti-cancer immune response, so the hypothesis of this trial is that the two medications will be more effective together. The control therapy consists of pembrolizumab, alone or in combination with a chemotherapy medication called capecitabine, which is the current standard of care. To study the effectiveness of each treatment, the researchers are following up with all participants to learn if and when their breast cancer returns.
摘要：
新辅助治疗后具有残留浸润性疾病的早期三阴性乳腺癌（TNBC）患者即使使用新辅助和pembrolizumab辅助治疗也具有很高的复发风险。Sacituzumabgovitecan,具有拓扑异构酶I抑制剂有效载荷的Trop-2定向抗体-药物缀合物，与化疗相比，治疗前转移性TNBC患者的无进展生存期（PFS）和总生存期（OS）改善。此外，临床前数据表明,拓扑异构酶I抑制剂可能通过激活cGAS-STING途径增强免疫检查点抑制剂的作用.在这里，我们描述了国际随机III期AFT-65/ASCENT-05/OptimICE-RD试验，该研究评估了在新辅助治疗后早期TNBC伴残留侵袭性疾病的患者中，sacituzumabgovitecan联合派姆单抗与医师选择的治疗（派姆单抗±卡培他滨）的疗效和安全性。临床试验注册：NCT05633654（ClinicalTrials.gov）其他研究ID号：Gilead研究ID：GS-US-595-6184注册日期：2022年12月1日研究开始日期：2022年12月12日招聘状态：招聘。
AFT-65/ASCENT-05/OptimICE-RD是一项正在进行的临床试验，正在测试II期或III期三阴性乳腺癌（TNBC）患者的新治疗组合。II-III期是指癌症局限于乳腺和/或附近的淋巴结，可以通过手术切除。然而,手术后癌症仍有复发的风险。为了降低这种风险，II-III期TNBC患者在手术前后接受抗癌药物治疗.对一些病人来说,手术前接受抗癌药物产生病理完全缓解（pCR），这意味着手术中没有可观察到的癌症。pCR患者的复发风险低于残留疾病患者。AFT-65/ASCENT-05/OptimICE-RD试验包括II-III期TNBC患者，他们在完成手术前抗癌药物治疗后有残留癌症。所有参与者的乳房和/或淋巴结都有任何剩余的癌症通过手术切除，之后，他们被随机分配接受两种治疗之一。实验疗法包括pembrolizumab和一种名为sacituzumabgovitecan的药物，直接杀死癌细胞，并可能增强抗癌免疫反应。Pembrolizumab增强了抗癌免疫反应，因此，这项试验的假设是两种药物一起使用会更有效。对照疗法包括pembrolizumab，单独或与称为卡培他滨的化疗药物联合使用，这是目前的护理标准。为了研究每种治疗方法的有效性，研究人员正在跟进所有参与者，以了解他们的乳腺癌是否以及何时复发。
AFT-65/ASCENT-05/OptimICE-RD是一项正在进行的临床试验，正在测试II期或III期三阴性乳腺癌（TNBC）患者的新治疗组合。II-III期是指癌症局限于乳腺和/或附近的淋巴结，可以通过手术切除。然而,手术后癌症仍有复发的风险。为了降低这种风险，II-III期TNBC患者在手术前后接受抗癌药物治疗.对一些病人来说,手术前接受抗癌药物产生病理完全缓解（pCR），这意味着手术中没有可观察到的癌症。pCR患者的复发风险低于残留疾病患者。AFT-65/ASCENT-05/OptimICE-RD试验包括II-III期TNBC患者，他们在完成手术前抗癌药物治疗后有残留癌症。所有参与者的乳房和/或淋巴结都有任何剩余的癌症通过手术切除，之后，他们被随机分配接受两种治疗之一。实验疗法包括pembrolizumab和一种名为sacituzumabgovitecan的药物，直接杀死癌细胞，并可能增强抗癌免疫反应。Pembrolizumab增强了抗癌免疫反应，因此，这项试验的假设是两种药物一起使用会更有效。对照疗法包括pembrolizumab，单独或与称为卡培他滨的化疗药物联合使用，这是目前的护理标准。为了研究每种治疗方法的有效性，研究人员正在跟进所有参与者，以了解他们的乳腺癌是否以及何时复发。
