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·714 · 南 京 医 科 大 学 学 报 2025年5月

（续表2）
Drugs
combined Clinical trial Efficacy Safety
with ADC
Phase Ⅲ HER2CLIMB⁃02 trial（NCT Median PFS was 9.5 months vs. The most common AE included nausea
03975647），T⁃DM1±tucatinib for pa⁃ 7.4 months for the tucatinib and （65.4% in the tucatinib arm vs. 49.4%
tients with previously treated HER2 ⁃ control arms，respectively，HR= in the control arm），diarrhea（56.7% vs.
positive LABC/mBC（n=463）：the tuca⁃ 0.759（95%CI：0.607-0.950，P= 26.6%）and fatigue（48.9% vs. 37.3%）
tinib arm（n=228）；the placebo arm（n= 0.016 3） The most common grade ≥3 AE in the
235） tucatinib arm was elevated alanine and
aspartate aminotransferase
Immune Phase Ⅱ KATE2 trial（NCT02924883），Median PFS was 8.2 months The most common grade ≥3 AE was
checkpoint T ⁃ DM1 ± atezolizumab for previously （95% CI：5.8-10.7）for patients thrombocytopenia（13% in the atezoli⁃
inhibitors treated，HER2 ⁃ positive advanced assigned atezolizumab versus zumab arm and 4% in the placebo arm）.
breast cancer（n=202）：the atezolizum⁃ 6.8 months（95% CI：4.0-11.1） Serious AE occurred in 33% of patients
ab arm（n=133）；the placebo arm（n= for those assigned placebo（HR= treated with atezolizumab and 19% of pa⁃
69） 0.82，95%CI：0.55-1.23；P=0.33） tients treated with placebo. One patient
receiving atezolizumab died from a treat⁃
ment⁃related adverse event（hemophago⁃
cytic syndrome）

Phase Ⅰb/Ⅱ BEGONIA trial（NCT Confirmed ORR was 79%（95% Grade 3/4 AE occurred in 17 patients
03742102），Arm 7：datopotamab de⁃ CI=67%- 88% ）；median PFS （36%），and severe AE occurred in 7 pa⁃
ruxtecan（Dato⁃DXd）+ durvalumab as was 13.8 months（95% CI：11- tients（15% ）.The most common all ⁃
first ⁃ line treatment for unresectable not calculable） Grade AE was gastrointestinal（nausea in

locally advanced/metastatic triple⁃neg⁃ 26 patients（55%）and stomatitis in 24
ative breast cancer（a/mTNBC）（n=62） patients（51%）
Phase Ⅱ SACI ⁃ IO HR + trial Median PFS was 8.4 months in The most frequent treatment⁃related toxi⁃
（NCT04448886），sacituzumab govite⁃ the sacituzumab govitecan+pem⁃ cities（≥G2）in the sacituzumab govite⁃
can ± pembrolizumab in patients with brolizumab arm vs. 6.2 months can+pembrolizumab arm were neutrope⁃
metastatic hormone receptor ⁃ positive/ in the sacituzumab govitecan arm nia（67.3%），fatigue（36.5%），alopecia
HER2 ⁃ negative breast cancer：the （HR=0.76，95% CI：0.47- 1.23； （36.5% ）and anemia（32.7% ）；in the
pembrolizumab arm（n=52）；the place⁃ P=0.26） sacituzumab govitecan arm，neutropenia
bo arm（n=52） （59.6%），alopecia（38.5%），diarrhea
（34.6%），nausea（32.7%）and fatigue
（32.7%）
AE：adverse event；CBR：clinical benefit rate；CI：confidence interval；CNS：central nervous system；ER：estrogen receptor；HER2：human epider⁃
mal growth factor receptor⁃2；HR：hazards ratio；LABC：locally advanced breast cancer；mBC：metastatic breast cancer；mPFS：median progression⁃free
survival；ORR：objective response rate；pCR：pathological complete response；RCB：residual cancer burden；a/mTNBC：unresectable locally advanced/
metastatic triple⁃negative breast cancer.

质降解 ADC（antibody⁃degrader conjugate，ADeC）、免 释放可以限制组织外毒性，降低 AE 发生率 ［45］ 。传
疫刺激 ADC（immune stimulating antibody conjugate， 统ADC采用随机偶联技术，其均一性差，稳定性低，
ISAC）和双载荷 ADC，其中 ADeC 因其高特异性、皮 影响药效及治疗窗。下一代 ADC 将引入非天然氨
摩尔级的效力以及能够针对肿瘤相关的细胞内蛋 基酸、工程化半胱氨酸以及N⁃糖基重构等方法实现
白而备受关注 ［51］ 。下一代连接子技术专注于控制 定点偶联 ［52-53］ 。
有效载荷的释放，而不依赖于内源性酶介导的裂解
4 小结与展望
作用。其中，“点击释放”技术能够通过触发分子的
点击化学反应来诱导药物的可控释放，受控的载荷 ADC通过其独特的结构设计，实现对肿瘤的精