Phase I/II study of the oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC).

医学 队列 肾细胞癌 内科学 肾透明细胞癌 恶心 临床终点 贫血 胃肠病学 不利影响 肿瘤科 临床研究阶段 泌尿科 外科 毒性 临床试验
作者
Toni K. Choueiri,Elizabeth R. Plimack,Todd M. Bauer,Jaime R. Merchan,Kyriakos P. Papadopoulos,David F. McDermott,M. Dror Michaelson,Leonard J. Appleman,Sanjay Thamake,Naseem J. Zojwalla,Eric Jonasch
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:38 (6_suppl): 611-611 被引量:37
标识
DOI:10.1200/jco.2020.38.6_suppl.611
摘要

611 Background: Hypoxia-inducible factor (HIF)-2α is a transcription factor that is a key oncogenic driver in RCC. MK-6482 is a first-in-class small molecule HIF-2α inhibitor that blocks the heterodimerization of HIF-2α with HIF-1β and induces regression in mouse xenograft RCC models. Methods: Pts with advanced ccRCC who had received at least 1 prior therapy were enrolled in an expansion cohort from the first-in-human phase 1/2 study of MK-6482 in advanced solid tumors (NCT02974738). Pts were administered 120 mg of MK-6482 orally once daily. Primary end point: safety. Key secondary end points: ORR, duration of response (DOR), and PFS. Results: Fifty-five pts were enrolled in the dose expansion cohort. Median (range) number of prior therapies was 3 (1-9); 67% received anti–PD-1 and anti-VEGF agents. Five pts (9%) were favorable risk, 40 (73%) were intermediate risk, and 10 (18%) were poor risk by IMDC criteria. With a median follow-up of 13 mo the most common all-grade, all-cause AEs > 30% were anemia (75%), fatigue (67%), dyspnea (47%), nausea (33%), and cough (31%). Anemia (26%) and hypoxia (15%) were the most common grade 3 AEs. No grade 4/5 drug-related AEs were observed. ORR was 24% with 13 confirmed PRs. Thirty-one pts (56%) had SD, with a disease control rate (CR+PR+SD) of 80%. Thirty-five of 52 (67%) pts with baseline and postbaseline assessments had tumor shrinkage. Median DOR was not reached; 81% of pts had response ≥6 mo per Kaplan-Meier estimate. Sixteen pts (29%) continued treatment beyond 12 mo. By IMDC risk, 2/5 pts with favorable risk had PR (ORR = 40%), 10/40 with intermediate risk had PR (ORR = 25%), and 1/10 with poor risk had PR (ORR = 10%); disease control rate was 100%, 80%, and 70%, respectively. Median PFS for the total population was 11.0 mo; the 12 mo PFS rate was 49%. Median PFS for favorable, intermediate, and poor IMDC risk was 16.5, 11.0, and 6.9 mo, respectively. As of May 15, 2019, 30 pts (55%) discontinued due to PD, 2 (4%) due to AEs. Sixteen pts (29%) had treatment ongoing. Conclusions: MK-6482 is well tolerated with a favorable safety profile and demonstrated promising single-agent activity in heavily pretreated pts with ccRCC across IMDC risk groups. A phase 3 trial in a similar population is planned. Clinical trial information: NCT02974738.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
量子星尘发布了新的文献求助10
1秒前
风信子完成签到,获得积分10
1秒前
小熊完成签到 ,获得积分10
3秒前
7秒前
shu完成签到,获得积分10
7秒前
7秒前
勤奋的毛豆完成签到,获得积分10
10秒前
行者无疆完成签到,获得积分10
10秒前
11秒前
Jackylee完成签到,获得积分10
11秒前
careyzhou发布了新的文献求助10
12秒前
舒心之云完成签到,获得积分10
14秒前
Desire发布了新的文献求助10
14秒前
独自受罪完成签到 ,获得积分10
15秒前
甘蓝型油菜完成签到,获得积分10
16秒前
Distance发布了新的文献求助10
17秒前
大橙子发布了新的文献求助10
18秒前
毛哥看文献完成签到 ,获得积分10
18秒前
Desire完成签到,获得积分10
20秒前
AiQi完成签到 ,获得积分10
21秒前
月月鸟完成签到 ,获得积分10
22秒前
陈永伟完成签到,获得积分10
24秒前
传奇3应助qq采纳,获得10
24秒前
feihua1完成签到 ,获得积分10
25秒前
大轩完成签到 ,获得积分10
26秒前
miemie66完成签到,获得积分10
27秒前
28秒前
Sun1c7完成签到,获得积分10
28秒前
大仁哥完成签到,获得积分10
28秒前
qqy完成签到,获得积分10
29秒前
失眠的香菇完成签到 ,获得积分10
31秒前
机灵的笼包完成签到,获得积分10
31秒前
兔子发布了新的文献求助10
32秒前
ohwhale完成签到 ,获得积分10
33秒前
chaotianjiao完成签到 ,获得积分10
34秒前
阳光的耳机完成签到,获得积分10
35秒前
K珑完成签到,获得积分10
35秒前
Solar energy完成签到,获得积分10
37秒前
鲤鱼青雪发布了新的文献求助10
38秒前
云淡风轻一宝完成签到,获得积分10
39秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038201
求助须知:如何正确求助?哪些是违规求助? 3575940
关于积分的说明 11373987
捐赠科研通 3305747
什么是DOI,文献DOI怎么找? 1819274
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022