抗体类癌症疗法在乳腺癌、影像诊断与淋巴瘤中展现前景

The combination of sacituzumab govitecan-hziy (Trodelvy) and pembrolizumab (Keytruda) significantly improved progression-free survival compared with chemotherapy plus pembrolizumab as a frontline treatment for patients with PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer (TNBC), according to findings from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) published in The New England Journal of Medicine.

在《The New England Journal of Medicine》发表的3期ASCENT-04/KEYNOTE-D19试验（NCT05382286）结果显示，与化疗联合pembrolizumab（Keytruda）相比，sacituzumab govitecan-hziy（Trodelvy）联合pembrolizumab作为一线治疗，显著延长了PD-L1阳性、局部晚期不可切除或转移性三阴性乳腺癌（TNBC）患者的无进展生存期（PFS）。

At a median follow-up of 14.0 months (range, 0.1-28.6), the median PFS as assessed by blinded independent central review (BICR) was 11.2 months (95% CI, 9.3-16.7) in the sacituzumab govitecan plus pembrolizumab arm (n = 221) compared with 7.8 months (95% CI, 7.3-9.3) in the chemotherapy plus pembrolizumab arm (n = 222; HR, 0.65; 95% CI, 0.51-0.84; P < .001). The 12-month PFS rate was 48% (95% CI, 41%-56%) in the investigational arm vs 33% (95% CI, 26%-40%) in the control arm. Overall survival (OS) data were immature at the time of the primary analysis.

在中位随访14.0个月（范围0.1-28.6）时，经盲法独立中心审查（BICR）评估，sacituzumab govitecan联合pembrolizumab组（n = 221）的中位PFS为11.2个月（95% CI, 9.3-16.7），而化疗联合pembrolizumab组（n = 222）为7.8个月（95% CI, 7.3-9.3；HR 0.65；95% CI, 0.51-0.84；P < .001）。12个月PFS率方面，试验组为48%（95% CI, 41%-56%），对照组为33%（95% CI, 26%-40%）。在主要分析时，总生存期（OS）数据尚不成熟。

This open-label, international trial enrolled adult patients with locally advanced unresectable or metastatic TNBC who had received no prior therapy for advanced disease and whose tumors were PD-L1–positive (defined as having a combined positive score [CPS] ≥ 10). Patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg intravenously (IV) on days 1 and 8 plus pembrolizumab at 200 mg IV on day 1 of each 21-day cycle, or physician's choice of chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab at 200 mg on day 1 of each 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or death. PFS by BICR served as the primary end point. Secondary end points included OS, objective response rate (ORR), duration of response (DOR), time to response (TTR), and safety.

这项开放标签的国际试验纳入局部晚期不可切除或转移性TNBC成人患者；这些患者此前未接受过针对晚期疾病的治疗，且肿瘤为PD-L1阳性（定义为综合阳性评分[CPS] ≥ 10）。患者按1:1随机分配，接受sacituzumab govitecan 10 mg/kg静脉注射（IV），于每个21天周期的第1天和第8天给药，并在每个21天周期第1天接受pembrolizumab 200 mg IV；或由研究者选择化疗方案（paclitaxel、nab-paclitaxel，或gemcitabine联合carboplatin）并在每个21天周期第1天给予pembrolizumab 200 mg。治疗持续至疾病进展、出现不可接受的毒性或死亡。BICR评估的PFS为主要终点；次要终点包括OS、客观缓解率（ORR）、缓解持续时间（DOR）、起效时间（TTR）及安全性。

Between October 17, 2022, and August 21, 2024, 443 patients were enrolled. The median age was 54 years (range, 23-88) in the sacituzumab govitecan arm vs 55 years (range, 27-82) in the chemotherapy arm. All patients were female and had PD-L1–positive disease, and most patients in the respective arms had an ECOG performance status of 0 (71% vs 69%). Disease status at random assignment in both arms included metastatic at initial diagnosis (34%), recurrent within 6 to 12 months after curative-intent treatment (18%), and recurrent more than 12 months after curative-intent treatment (48%).

在2022年10月17日至2024年8月21日期间，共入组443例患者。sacituzumab govitecan组的中位年龄为54岁（范围23-88），化疗组为55岁（范围27-82）。所有患者均为女性且为PD-L1阳性；两组多数患者的ECOG体能状态评分为0分（分别为71% vs 69%）。两组在随机分配时的疾病状态包括：初诊即为转移性（34%）、根治意图治疗后6至12个月内复发（18%）、根治意图治疗后超过12个月复发（48%）。

The ORR was 60% (95% CI, 53-66) in the sacituzumab govitecan plus pembrolizumab group, including a complete response (CR) rate of 13% and a partial response (PR) rate of 47%. In the chemotherapy plus pembrolizumab group, the ORR was 53% (95% CI, 46-60; OR, 1.3; 95% CI, 0.9-1.9), with a CR rate of 8% and a PR rate of 45%. Among responders, the median DOR was significantly longer with sacituzumab govitecan plus pembrolizumab, at 16.5 months (95% CI, 12.7-19.5) compared with 9.2 months (95% CI, 7.6-11.3) in the chemotherapy arm. The median TTR was 1.9 months in both treatment groups. Subgroup analyses showed that the PFS benefit with the antibody-drug conjugate (ADC)–based combination was consistent across predefined patient subgroups, including age, geographic region, and disease status.

sacituzumab govitecan联合pembrolizumab组的ORR为60%（95% CI, 53-66），其中完全缓解（CR）率为13%，部分缓解（PR）率为47%。化疗联合pembrolizumab组的ORR为53%（95% CI, 46-60；OR 1.3；95% CI, 0.9-1.9），其中CR率为8%，PR率为45%。在应答者中，sacituzumab govitecan联合pembrolizumab的中位DOR显著更长，为16.5个月（95% CI, 12.7-19.5），而化疗组为9.2个月（95% CI, 7.6-11.3）。两组的中位TTR均为1.9个月。亚组分析显示，这一基于抗体药物偶联物（ADC）的联合方案在预先定义的各患者亚组（包括年龄、地理区域及疾病状态）中均表现出一致的PFS获益。

In separate research, investigators at the University of Missouri developed a very small antibody that seeks out EphA2, a protein frequently present in cancer tumors. They radioactively labeled the antibody to make it visible during positron emission tomography (PET) scans. In experiments using mice, this cancer detecting approach clearly illuminated tumors that produced EphA2. The results suggest that tagging the antibody could help doctors detect cancers that contain this protein and determine which patients might respond to therapies designed to target EphA2-positive tumor cells while leaving healthy tissue unharmed.

在另一项研究中，University of Missouri的研究人员开发了一种非常小的抗体，可识别并靶向EphA2——一种在癌症肿瘤中常见的蛋白。他们对该抗体进行了放射性标记，使其在正电子发射断层扫描（PET）中可见。在小鼠实验中，这种癌症检测方法能够清晰显像表达EphA2的肿瘤。结果提示，通过对抗体进行标记，可能帮助医生检测含有该蛋白的癌症，并判断哪些患者可能对旨在靶向EphA2阳性肿瘤细胞、同时尽量不伤害健康组织的治疗产生应答。

The new targeted approach is noninvasive, and results from the imaging can be obtained in hours rather than days. Doctors currently depend on biopsies and MRI scans to evaluate tumors in cancer patients. These methods can be invasive, require significant time, and often provide limited insight into the specific proteins found within cancer cells. The study, titled "Preclinical evaluation of anti-EphA2 minibody-based immunoPET agent as a diagnostic tool for cancer," was published in Molecular Imaging and Biology.

这种新的靶向方法为无创检查，影像结果可在数小时内获得，而非数天。目前医生评估癌症患者肿瘤多依赖活检与MRI检查；这些方法可能具有侵入性、耗时较长，并且往往难以充分揭示癌细胞内存在的特定蛋白。该研究题为“Preclinical evaluation of anti-EphA2 minibody-based immunoPET agent as a diagnostic tool for cancer”，发表于《Molecular Imaging and Biology》。

Data from a real-world multicenter analysis shared during the 2026 Transplantation and Cellular Therapy Meetings suggested that CD20-targeted bispecific antibodies (BsAbs) had activity after CD19-targeted CAR T-cell therapy in patients with mantle cell lymphoma, although longer follow-up is needed to understand the durability of response.

在2026年Transplantation and Cellular Therapy Meetings上公布的一项真实世界多中心分析数据显示，在套细胞淋巴瘤患者接受CD19靶向CAR T细胞治疗后，CD20-targeted bispecific antibodies（BsAbs）仍显示出一定活性，但仍需更长随访以评估缓解的持久性。

In the entire cohort (n = 20), the objective response rate achieved with BsAbs was 70%, which included a complete response (CR) rate of 45%. At a median follow-up of 8.9 months, the median duration of response (DOR) had not yet been reached (NR), the median progression-free survival (PFS) was 8.9 months, and the median overall survival was also NR.

在全队列（n = 20）中，BsAbs治疗获得的ORR为70%，其中CR率为45%。在中位随访8.9个月时，中位DOR尚未达到（NR），中位PFS为8.9个月，中位OS亦为NR。

When broken down further, those who received mosunetuzumab-axgb (Lunsumio)/polatuzumab vedotin-piiq (Polivy; n = 9) achieved an ORR of 76% with a CR rate of 56% with BsAbs. At a median follow-up of 8.9 months, the median DOR was 7.5 months, the median PFS was 8.9 months, and the median OS was NR. Those who received glofitamab-gxbm (Columvi; n = 11) experienced an ORR of 64%, which included a CR rate of 36% with BsAbs. At a median follow-up of 8.9 months, the median DOR, PFS, and OS were all NR. In those who received brexucabtagene autoleucel (Tecartus; brexu-cel; n = 10), the ORR was 60%, and the CR rate was 50%; at a median follow-up of 12.7 months, the median DOR was NR, the median PFS was 4.3 months, and the median OS was NR.

进一步分层显示，接受mosunetuzumab-axgb（Lunsumio）/polatuzumab vedotin-piiq（Polivy；n = 9）的患者，BsAbs治疗的ORR为76%，CR率为56%。在中位随访8.9个月时，中位DOR为7.5个月，中位PFS为8.9个月，中位OS为NR。接受glofitamab-gxbm（Columvi；n = 11）的患者，BsAbs治疗的ORR为64%，其中CR率为36%。在中位随访8.9个月时，中位DOR、PFS与OS均为NR。接受brexucabtagene autoleucel（Tecartus；brexu-cel；n = 10）的患者，ORR为60%，CR率为50%；在中位随访12.7个月时，中位DOR为NR，中位PFS为4.3个月，中位OS为NR。

Additional data indicated that outcomes were inferior among patients who experienced early relapse after CAR T exposure (n = 10). In these patients, the median DOR was 7.5 months, the median PFS was 3.3 months, and the median OS was 7.6 months. In comparison, those with late relapse to CAR T (n = 10) experienced a median DOR (P = .57), PFS (P = .065), and OS (P = .13) that was NR.

补充数据显示，在CAR T治疗后早期复发的患者（n = 10）中，结局更差：中位DOR为7.5个月，中位PFS为3.3个月，中位OS为7.6个月。相比之下，CAR T治疗后晚期复发的患者（n = 10）的中位DOR（P = .57）、PFS（P = .065）与OS（P = .13）均为NR。

The retrospective multicenter study assessed the use of BsAbs in those who were diagnosed with mantle cell lymphoma and who were receiving treatment at 10 medical centers throughout the United States. Of the 31 total patients with this disease who received treatment at the centers that comprised the Collaborative US Bispecific Consortium, 20 were administered BsAbs post CAR T-cell therapy and were included in the analysis. In the entire cohort of 20 patients, the median age was 64 years (range, 48-85), and most were male (80%). The median ECOG performance status of patients was 1 (range, 0-3). Moreover, patients were fairly heavily pretreated, having received a median of 5 prior lines of therapy (range, 2-9).

这项回顾性多中心研究评估了在美国10家医疗中心接受治疗的套细胞淋巴瘤患者中，BsAbs的应用情况。在Collaborative US Bispecific Consortium所涵盖中心接受治疗的31例该病患者中，有20例在CAR T细胞治疗后接受了BsAbs，并纳入分析。在这20例患者的全队列中，中位年龄为64岁（范围48-85），多数为男性（80%）。患者的ECOG体能状态中位数为1分（范围0-3）。此外，患者既往治疗较为充分，既往治疗线数中位数为5线（范围2-9）。