2020胃肠道肿瘤免疫治疗新进展(最新推荐)

Before start of the study
= Nivolumab administration = Tumor response assessment
Treatment phase
N = 64
Until PD or unacceptable toxicity
Follow-up phase
Observe 4 weeks later
Best Overall Response ORR (PR)
SD
PD
Total: n=23
7
2
13
%
30% (13-53) 9% (1-28)
56% (34-77)
Toshihiko Doi at 2016 ASCO Annual Meeting
Nivo治疗食管癌-ONO‐4538-07 (ATTRACTION-1)
(入组中)
Columbia Univ NCT02710396
(入组中)
Washington Univ
NCT02642809 (入组中)
Duke Univ NCT03064490
(尚未启动)
Dana Farber NCT02971956
(尚未入组)
试验分 期
人群
2
胃癌, 食管胃结合 部癌, 或食管腺癌
2
局部晚期EC
2
食管鳞癌
转移性食管癌、胃
2
癌或食管胃结合部
癌
2
食管鳞癌、其他
1
转移性食管癌
2
食管癌和胃癌
2
难治性晚期食管癌
随机化
• P 200 mg q3w+ CRS-207
CT序贯化放疗 +P 200 mg q3w. 手术后给予
P200mg Q3W， 新辅助化放疗：CT， pembrolizumab 和放 疗. 给予手术，手术后 给予P 200 mg q2w 每日给予姑息性外照射 放疗+P 200 mg q3w
11 (17.2)
[9.9–28.2]
Time to response, median (min–max), months
—
1.45 (1.4–3.0)
Duration of response, median (95% CI), months
—
11.17 (3.02 to —)
Progression-free survival, median (95% CI), months Overall survival, median (95% CI), months
Pembro在转移性EAC或ESCC中的2期KEYNOTE-180研究
KEYNOTE-181: Phase 3, open-label study of second-line pembrolizumab vs single-agent chemotherapy in patients
with advanced/metastatic esophageal adenocarcinoma
P 200 mg q3w
• Pembrolizumab +近 距离放疗
P 200 mg q3w
• P 200 mg q3w
N 主要终点 次要终点
79
治疗相关不良 事件
肿瘤缓解、生 存、免疫应答、
生物标记物
CR, R0切除率,
2 (3.1)
[0.9–10.7]
3 (4.7)
[1.6–12.9]
Partial response (PR)
12 (18.8)
[11.1–30.0]
8 (12.5)
[6.5–22.8]
Stable disease (SD)
20 (31.3)
[21.2–43.4]
16 (25.0)
[16.0–36.8]
胃肠肿瘤免疫治疗新进展
首个完全缓解的患者-MSI CRC
主要内容
• 食管癌免疫治疗数据 • 胃癌免疫治疗数据 • 肠癌免疫治疗数据 • 可能预测疗效的指标：PD-L1，POLE，TMB，EBV，
MSI/dMMR，HLA，肠道菌群，肝转移等 • 展望
KEYNOTE-028: Phase 1b Pembro for PD-L1 positive
Checkmate 473: Phase 3, open-label study of second-line Nivolumab vs single-agent chemotherapy in patients with
advanced/metastatic esophageal adenocarcinoma
Progressive disease (PD)
29 (45.3)
—
29 (45.3)
—
Not evaluable (NE)
1 (1.6)
—
8 (12.5)b
—
Overall objective response (CR + PR), n (%) [95% CI]
14 (21.9)
[13.5–33.4]
0
2
4
6 weeks
Other responses
Repeat this cycle of treatment and assessment
N = 64
Best overall response/ORR, n (%) [95%CI]
Investigator review
Central review
Complete response (CR)
二线Nivol对比化疗治疗EAC的3期Checkmate-473研究
Pembrolizumab for previously treated metastatic adenocarcinoma or squamoous cell carcinoma of the
esophagus: Phase 2 KEYNOTE-180 study.
二线Pembro对比单药化疗治疗mEAC3期KEYNOTE-181研究
食管癌研究-ongoing
研究
Aduro Biotech NCT03122548
(入组中)
Cornell Univ NCT02998268
(入组中)
Βιβλιοθήκη BaiduYonsei Univ NCT02844075
(入组中)
City of Hope NCT02830594
—
1.51 (1.41–2.83)
10.78 (7.39–13.34)
SHR-1210在食管鳞癌中的I期临床研究
• 常规治疗失败的晚期食管癌 • ORR：33.3%，中位PFS：3.6个月
Clin Cancer Res. 2018 Jan 22.CCR-17-2439.
食管癌研究-ongoing