DART/SWOG/NCI phase II anti-CTLA-4/PD-1 trial: clear cell carcinomas of ovary, endometrium, cervix.
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Chae Young Kwang, Othus Megan, Patel Sandip P, Backes Floortje J, O'Malley David M, Cristea Mihaela, Naing Aung, Kurnit Katherine, Eskander Ramez N, T Goodrich Scott, Robinson William R, Scalici Jennifer, Chan John, Ali-Ahmad Hussein, Hays John, McCormick Colleen, Kim Edward J, Sueblinvong Thanasak, Ahmed Amina, Siedel Jean, Thomes Pepin Jessica, Bottsford-Miller Justin Neal, Fagbemi Seth Olusegun, Jaslowski Anthony John, Kim Hye Sung, Chung Liam Il-Young, Moloney-Lineen Carolyn, McLeod Christine M, Chen Helen X, Sharon Elad, Streicher Howard, Ryan Christopher W, Blanke Charles D, Kurzrock Razelle
Аннотация
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 iRECIST and 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.
TRIAL REGISTRATION NUMBER: NCT02834013.