DART/SWOG/NCI phase II anti-CTLA-4/PD-1 trial - clear cell carcinomas of ovary, endometrium, cervix

Sep 22, 2026

Uploaded by Oliver

Dual anti-CTLA-4/PD-1 therapy was evaluated in a multicenter phase II DART study for gynecologic clear cell carcinomas (CCCs), a rare and aggressive group with limited options. Ipilimumab 1 mg/kg every 6 weeks plus nivolumab 240 mg every 2 weeks targeted RECIST overall response rate (ORR) with immune-based ORR, iRECIST, progression-free survival, overall survival, clinical benefit rate, and toxicity. In 32 patients, ORR was 9.38% by RECIST and 12.5% including iRECIST; durable ovarian complete responses were observed, with median OS 21.7 months and no treatment-related deaths.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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ABSTRACT

Background

Methods

Results

Conclusions

WHAT IS ALREADY KNOWN ON THIS TOPIC

WHAT THIS STUDY ADDS

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

BACKGROUND

Open access Original research DART/SWOG/NCI phase II antiCTLA-4/PD-1 trial: clear cell carcinomas of ovary, endometrium, cervix Young Kwang Chae ,1 Megan Othus ,2 Sandip P Patel,3 Floortje J Backes,4 David M O’Malley,4 Mihaela Cristea,5 Aung Naing ,6 Katherine Kurnit,7 Ramez N Eskander,3 Scott T Goodrich,8 William R Robinson,9 Jennifer Scalici,10 John Chan,11 Hussein Ali-Ahmad,12 John Hays,4 Colleen McCormick,13 Edward J Kim,14 Thanasak Sueblinvong,15 Amina Ahmed,16 Jean Siedel,17 Jessica Thomes Pepin,18 Justin Neal Bottsford-Miller,19 Seth Olusegun Fagbemi,20 Anthony John Jaslowski,20 Hye Sung Kim,1,21 Liam Il-Young Chung,1 Carolyn Moloney-Lineen,1 Christine M McLeod,22 Helen X Chen,23 Elad Sharon,23 Howard Streicher,23 Christopher W Ryan,24 Charles D Blanke,25 Razelle Kurzrock26 To cite: Chae YK, Othus M, Patel SP, et al. DART/SWOG/NCI phase II anti-CTLA-4/PD-1 trial: clear cell carcinomas of ovary, endometrium, cervix. Journal for ImmunoTherapy of Cancer 2026;14:e012805 . doi:10 . 1136/ jitc-2025-012805 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2025-012805](jitc-2025-012805)) . YKC and SPP contributed equally. Accepted 20 January 2026 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Dr Young Kwang Chae; [chaelabmeeting@gmail.com](chaelabmeeting@gmail.com) Dr Sandip P Patel; [patel@ucsd.edu](patel@ucsd.edu) Dr Razelle Kurzrock; [rkurzrock@mcw.edu](rkurzrock@mcw.edu) ABSTRACT Background Dual anti-CTLA-4/PD-1 inhibitors show efficacy in numerous malignancies. We are the first to report on the efficacy of ipilimumab-nivolumab immunotherapy ina dedicated cohort of patients with gynecologic clear cell carcinomas (CCCs), which are rare, aggressive cancers. Methods DART is a multicenter, multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks), with primary objective as Response Evaluation Criteria in Solid Tumors (RECIST)-based overall response rate (ORR) . Secondary objectives were ORR by immune RECIST (iRECIST), progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; overall response plus stable disease (SD) ≥6 months), and toxicity. Results Overall, in this cohort of 32 patients with gynecologic CCC (N=19 ovarian, N=8 endometrial, N=5 cervical; 1–8 prior therapies; 3 had prior PD-1 inhibitor exposure), an ORR of 9 .38% was seen. This included two complete responses (CRs) (both ovarian origin) that are ongoing at >3 years and one partial response (PR) . Overall ORR increased to 12.5% when including one PR by iRECIST criteria for a patient with cervical CCC lasting 26 months, with an OS of 32.0 months. The CBR was 21.88% overall for all 32 (7/32) evaluable patients with gynecologic CCC. This included two CR, one PR, and two patients with SD >6 months with ovarian CCC and one PR by iRECISTand one SD >6 months in two patients with cervical CCC. PFS for the seven patients with CBR was 63 .6+, 47 .8+, 40.5+, 50 .8+, 7 .4, 26, and 58. 1+ months. Median OS was 21.7 months for all 32 evaluable patients. Seven of 32 patients (21.9%) discontinued therapy because of toxicity; there were no treatment-related deaths. Conclusions Ipilimumab plus nivolumab demonstrated durable antitumor activity in certain patients with CCC of gynecological origin, particularly in those with CCC of ovarian origin. Safety is consistent with the known profile of ipilimumab and nivolumab. Correlative studies to better identify which patients will respond to combined ipilimumab and nivolumab are ongoing. WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Gynecologic clear cell carcinomas (CCCs) are rare, aggressive cancers wit

FAQs

该研究的主要研究目的是什么？

主要研究目的为基于 RECIST 的总体缓解率（ORR）。

研究的治疗方案如何设计？

DART 试验采用多中心、多队列设计，使用 ipilimumab 与 nivolumab 联合：ipilimumab 1 mg/kg 每 6 周静脉给药，nivolumab 240 mg 每 2 周静脉给药。

该队列中总体缓解率与生存结论是什么？

在 32 名患者中，RECIST 总体缓解率为 9.38%，纳入 iRECIST 后为 12.5%；中位总生存期为 21.7 个月，且未出现与治疗相关的死亡。

Sep 22, 2026

Uploaded by Oliver